Tissue penetration device

ABSTRACT

A tissue penetration device and method of using same. The tissue penetration device may optionally include sampling and analyzing functions, which may be integrated. An embodiment provides control of a lancet used for sampling blood. Electric field coils or solenoids may drive the lancet using electromagnetic force. Advancement and retraction of a lancet may be controlled by a feedback loop monitoring the position and velocity of the lancet embodiments of the lancet driver can be configured to follow a predetermined tissue lancing profile. Embodiments of the invention include a lancet and method for using a lancet to maintain the patency of the wound tract once the lancet has cut into the skin.

RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 10/127,395, filedApr. 19, 2002, now U.S. Pat. No. 7,025,774, which application is fullyincorporated by reference herein.

BACKGROUND

Lancing devices are known in the medical health-care products industryfor piercing the skin to produce blood for analysis. Biochemicalanalysis of blood samples is a diagnostic tool for determining clinicalinformation. Many point-of-care tests are performed using whole blood,the most common being monitoring diabetic blood glucose level. Otheruses for this method include the analysis of oxygen and coagulationbased on Prothrombin time measurement. Typically, a drop of blood forthis type of analysis is obtained by making a small incision in thefingertip, creating a small wound, which generates a small blood dropleton the surface of the skin.

Early methods of lancing included piercing or slicing the skin with aneedle or razor. Current methods utilize lancing devices that contain amultitude of spring, cam and mass actuators to drive the lancet. Theseinclude cantilever springs, diaphragms, coil springs, as well as gravityplumbs used to drive the lancet. Typically, the device is. pre-cocked orthe user cocks the device. The device is held against the skin and theuser, or pressure from the users skin, mechanically triggers theballistic launch of the lancet. The forward movement and depth of skinpenetration of the lancet is determined by a mechanical stop and/ordampening, as well as a spring or cam to retract the lancet. Suchdevices have the possibility of multiple strikes due to recoil, inaddition to vibratory stimulation of the skin as the driver impacts theend of the launcher stop, and only allow for rough control for skinthickness variation. Different skin thickness may yield differentresults in terms of pain perception, blood yield and success rate ofobtaining blood between different users of the lancing device.

Success rate generally encompasses the probability of producing a bloodsample with one lancing action, which is sufficient in volume to performthe desired analytical test. The blood may appear spontaneously at thesurface of the skin, or may be “milked” from the wound. Milkinggenerally involves pressing the side of the digit, or in proximity ofthe wound to express the blood to the surface. The blood dropletproduced by the lancing action must reach the surface of the skin to beviable for testing. For a one-step lance and blood sample acquisitionmethod, spontaneous blood droplet formation is requisite. Then it ispossible to interface the test strip with the lancing process formetabolite testing.

When using existing methods, blood often flows from the cut bloodvessels but is then trapped below the surface of the skin, forming ahematoma. In other instances, a wound is created, but no blood flowsfrom the wound. In either case, the lancing process cannot be combinedwith the sample acquisition and testing step. Spontaneous blood dropletgeneration with current mechanical launching system varies betweenlauncher types but on average it is about 50% of lancet strikes, whichwould be spontaneous. Otherwise milking is required to yield blood.Mechanical launchers are unlikely to provide the means for integratedsample acquisition and testing if one out of every two strikes does notyield a spontaneous blood sample.

Many diabetic patients (insulin dependent) are required to self-test forblood glucose levels five to six times daily. Reducing the number ofsteps required for testing would increase compliance with testingregimes. A one-step testing procedure where test strips are integratedwith lancing and sample generation would achieve a simplified testingregimen. Improved compliance is directly correlated with long-termmanagement of the complications arising from diabetes includingretinopathies, neuropathies, renal failure and peripheral vasculardegeneration resulting from large variations in glucose levels in theblood. Tight control of plasma glucose through frequent testing istherefore mandatory for disease management.

Another problem frequently encountered by patients who must use lancingequipment to obtain and analyze blood samples is the amount of manualdexterity and hand-eye coordination required to properly operate thelancing and sample testing equipment due to retinopathies andneuropathies particularly, severe in elderly diabetic patients. Forthose patients, operating existing lancet and sample testing equipmentcan be a challenge. Once a blood droplet is created, that droplet mustthen be guided into a receiving channel of a small test strip or thelike. If the sample placement on the strip is unsuccessful, repetitionof the entire procedure including re-lancing the skin to obtain a newblood droplet is necessary.

What is needed is a device, which can reliably, repeatedly andpainlessly generate spontaneous blood samples. In addition, a method forperforming analytical testing on a sample that does not require a highdegree of manual dexterity or hand-eye coordination is required.Integrating sample generation (lancing) with sample testing (sample totest strip) will result in a simple one-step testing procedure resultingin better disease management through increased compliance with selftesting regimes.

SUMMARY

Advantages can be achieved by use of a tissue penetration device thathas user definable control of parameters such as lancet displacement,velocity of incision, retraction, acceleration, and tissue dwell time. Adevice having features of the invention can compensate for long-termchanges in skin physiology, nerve function, and peripheral vascularperfusion such as occurs in diabetes, as well as diurnal variation inskin tensile properties. Alternatively, a device having features of theinvention can compensate for skin differences between widely differingpopulations such as pediatric and geriatric patients, in addition toreducing the pain associated with lancing.

An embodiment of the invention is directed to a lancing device, whichcontrols the advancement and retraction of a lancet by monitoring theposition of the lancet in conjunction with a velocity control system inthe form of a feedback loop. The feedback loop can modulate the lancetdriver to follow a predetermined velocity versus position profile. Theadvancement and retraction profiles of the lancet through the skingovern the pain, success and spontaneous generation of the blood sample.Such a tissue penetration device can be combined with a sampling module,or sampling module cartridge, that contains a plurality of samplingmodules. By integrating the tissue penetration function with the sampleacquisition, and, (optionally), sample analysis, user convenience can begreatly enhanced as well as other advantages.

In another embodiment of the invention, a tissue penetration deviceincludes a tissue penetration element coupled to a controllable driver.The controllable driver may include a magnetic source that produces acontrollable magnetic field in a magnetically active region adjacent themagnetic source. A magnetic member disposed at least partially in themagnetically active region is coupled to the tissue penetration element.A position sensor is configured to measure the position of the tissuepenetration element. The tissue penetration element can be a lancet.

In yet another embodiment of the invention, a controllable driverincludes a magnetic source that produces a controllable magnetic fieldin a magnetically active region adjacent the magnetic source. A magneticmember is disposed at least partially in the magnetically active regionand configured to be coupled to a lancet. A position sensor isconfigured to measure the position of the magnetic member. A processoris electrically coupled to the magnetic source and configured to controlthe magnitude of the magnetic field by controlling the amount of timethe magnetic source is on in the magnetically active region based onfeedback from the position sensor.

Another embodiment of the invention is directed to a tissue penetrationdevice that includes a flat coil controllable driver having a magneticsource that produces a first magnetic field in a first magneticallyactive region and a second magnetic field in a second magneticallyactive region. A flat coil is secured to a translation substrate and hasa leading segment disposed at least partially within the firstmagnetically active region and a trailing segment disposed at leastpartially within the second magnetically active region. A tissuepenetration element is configured to penetrate tissue and mechanicallycoupled to the translation substrate. A position sensor is configured tomeasure the position of the tissue penetration element.

In yet another embodiment, the magnetically active regions areconstructed from collections (2 or more) of solenoid coils, allowingcoils to be energized such that the “slug” is always at least half (or⅔, ¾, etc.) within the active portion of the solenoid, ensuring that theforce exerted is always near optimal.

In an alternative embodiment, a tissue penetration device includes acontrollable driver that has a magnetic source that produces a magneticfield in a magnetically active region. A cylindrical coil is secured toa translation substrate and disposed at least partially within themagnetically active region. A tissue penetration element configured topenetrate tissue is mechanically coupled to the translation substrate. Aposition sensor is configured to measure the position of the tissuepenetration element directly or indirectly.

In an embodiment of a method of lancing for obtaining a sample of bloodfrom a patient, a tissue penetration device for obtaining a blood samplefrom a patient is provided. The tissue penetration device has a magneticsource that produces a controllable magnetic field in a magneticallyactive region adjacent the magnetic source. A magnetic member isdisposed at least partially in the magnetically active region and atissue penetration element is coupled to the magnetic member. Next, thetissue penetration device is disposed adjacent tissue of the patient.The magnetic source is then activated to produce a magnetic field in themagnetically active region generating a magnetic force between themagnetic field and the magnetic member and driving the tissuepenetration element into the patient's tissue.

In some embodiments, the magnetic field produced by the magnetic sourceis reversed after the tissue penetration element has entered thepatient's tissue, reversing the force on the tissue penetration elementand withdrawing the tissue penetration element from the patient'stissue. In addition, in other embodiments of the method, the magnitudeof the magnetic force on the magnetic member during penetration of thepatient's tissue by the tissue penetration element is greater than themagnitude of the magnetic force on the magnetic member during withdrawalof the tissue penetration element from the patient's tissue. In thisway, the tissue penetration element may be withdrawn at a lower velocityfrom the patient's tissue than a velocity of the tissue penetrationelement during penetration of the patient's tissue.

Advantages can be achieved in a tissue penetration device for bloodsampling by integrating a lancing and blood sample collection procedureso that the device can capture and transport the capillary blood fromthe wound created by the lancet or other tissue penetration element to adesired analytical area, such as a strip for analyzing glucose. This canbe done in embodiments of the invention by integrating the lancet,sample flow channel and reservoir into a disposable sampling module,which can be inserted into a tissue penetration sampling device withinstrumentation for analyzing the blood sample.

In the use of an embodiment of the invention, a finger is placed over anergonomically contoured sampling area and pressure is applied with thefinger so that a sensor will activate a driver, which will, in turn,lance the finger and allow the blood sample to be collected in thesample flow channel and transported to the reservoir for analysis in asingle step from the patient's perspective.

Once a sample has been obtained and transported to a reservoir,advantages can be achieved by using devices and methods for easilymeasuring the zero or start-time of an assay and applying such atechnology to kinetic assays. In addition, advantages can be achieved byusing devices and methods that accurately detect successful sampleintroduction into a sampling module, to detect sample arrival at anypredefined point or local environment in a sample flow channel, todetect sample arrival at a particular sensor or array of sensors, or toperform similar functions for fluids that are not samples containing theanalyte to be measured, e.g., subsequent reagents or wash fluids.Embodiments of the invention generally relate to a method for using athermal sensor to detect the presence or arrival of a fluid. Embodimentsof the invention use the signal obtained from a thermal sensor to definethe zero or start time of an assay for which knowing the rate ofreaction is important or useful.

In some embodiments, a first signal from the thermal sensor is readprior to arrival of the fluid, a second signal is read as the fluidarrives, and the first signal and the second signal are related toprovide an indicator that the fluid has arrived. In another embodiment,the method comprises determining the temperature of the localenvironment at the thermal sensor before the fluid arrives, determiningthe temperature of the local environment at the thermal sensor as thefluid arrives, and calculating the thermal differential, which may beused to indicate the arrival of the fluid.

Other embodiments of the invention can allow acquisition of the bloodsample seamlessly, that is, without substantial contamination fromambient air, such that the blood sample may be analyzed accurately forgaseous components such as oxygen and carbon dioxide. Sampled blood canbe acquired and transported to an analysis or storage device withoutsubstantial contamination by ambient air.

In one embodiment, a surface treatment of a support material is used onthe target tissue to engender a difference in wetting ability. Inanother embodiment, an active pumping device is used in addition tocapillary forces for drawing the blood into the sample reservoir and fordispensing blood from the reservoir to additional sites. Anotherembodiment includes the use of a device which compensates for aninadequate sample volume in the first sample reservoir by isolating thefirst sample reservoir and triggering a second lancing and acquisitionstep to fill a second “back-up” sample reservoir. Any of these threeembodiments can be used alone, or in any combination of the other twoembodiments.

User convenience as well as other advantages can be achieved with theuse of a sampling cartridge containing a plurality of sampling modulescapable of being used multiple times and obtaining multiple analyticalreadings before being discarded. Simplified actuation, lancing, sampleacquisition, testing, and readout, can all be provided in a handheldapparatus capable of multiple uses on one sampling module cartridge. Asampling cartridge embodiment contains many individual sampling modules,each of which allows the collection and testing of a sample of blood.This allows the sampling cartridge to be used numerous times beforeexchange with a new cartridge and disposal of the used cartridge becomesnecessary, thus reducing the need to dispose of used materials aftereach test. The sampling cartridge embodiment also retains used samplingmaterials safely, thereby reducing the problem of handling biohazardousmaterials.

In yet another embodiment, the sampling module can be configured tocontain a hypodermic (patent) needle, and drug delivery chamber.Inherent in the position control mechanism of the electronic actuator isthe ability to precisely define the position in space, allowing finiteplacement of a hypodermic syringe in the skin for injection of drugs,vaccines or the like. The reservoir for the drug or vaccine to beinjected is the polymeric needle support module. Drug delivery can bediscrete or continuous depending on the need.

A sampling cartridge embodiment provides for a simplified blood samplingand analysis process by having fewer components requiring assembly bythe user and reducing the frequency that the components must beassembled for testing. A single sampling module combines the lancet andsample reservoir with analytical region, reducing the task of assemblyby the user. The sampling cartridge combines a plurality of suchsampling modules in a unit package that fits cassette-like into a readerdevice. This multi-use sampling cartridge need only be removed andreplaced after all of the sampling modules are used, further reducingthe task of assembly, disassembly, and disposal by the user. In onepossible configuration, a separate apparatus provides a driver. In otherembodiments the driver is included in the analyzer device or isintegrated directly on the sampling module.

In a method, a series of blood samples may be collected and tested usinga single disposable sampling cartridge which is designed to couple to ananalyzer that can include a processor configured to interpret raw datafrom analyzed region. The sampling cartridge has a plurality of samplingmodules, each sampling module adapted to be used for a single bloodsampling cycle. The method starts with coupling of the samplingcartridge and analyzer and then initiating a blood sampling cycle. Uponcompletion of the blood sampling cycle, the sampling cartridge isadvanced to bring a fresh, unused sampling module online, ready toperform another blood sampling cycle. After a series of blood samplingcycles has been performed, the sampling cartridge is decoupled from theanalyzer and discarded, leaving the analyzer ready to be coupled with anew sampling cartridge.

In accordance with some embodiments of the invention, a method forlancing uses a lancet, a helix, or an elastomer to maintain the patencyof the wound tract once the lancet has cut into the skin. If penetrationtakes place, and an appropriate number of blood vessels are cut, bloodis allowed to flow up through the wound tract and onto the surface ofthe skin because the lancet, the helix, or the elastomer coats or bracesthe wound tract, keeping it open and patent. Coating or bracing isdefined generally as keeping the wound open so that the blood can reachthe surface of the finger. The term flow control can include any meansfor bracing the wound tract created by the lancet.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1-3 are graphs of lancet velocity versus position for embodimentsof spring driven, cam driven, and controllable force drivers.

FIG. 4 illustrates an embodiment of a controllable force driver in theform of a flat electric lancet driver that has a solenoid-typeconfiguration.

FIG. 5 illustrates an embodiment of a controllable force driver in theform of a cylindrical electric lancet driver using a coiled solenoid-type configuration.

FIG. 6 illustrates a displacement over time profile of a lancet drivenby a harmonic spring/mass system.

FIG. 7 illustrates the velocity over time profile of a lancet driver bya harmonic spring/mass system.

FIG. 8 illustrates a displacement over time profile of an embodiment ofa controllable force driver.

FIG. 9 illustrates a velocity over time profile of an embodiment of acontrollable force driver.

FIG. 10 illustrates the lancet needle partially retracted, aftersevering blood vessels; blood is shown following the needle in the woundtract.

FIG. 11 illustrates blood following the lancet needle to the skinsurface, maintaining an open wound tract.

FIG. 12 is a diagrammatic view illustrating a controlled feed-back loop.

FIG. 13 is a graph of force vs. time during the advancement andretraction of a lancet showing some characteristic phases of a lancingcycle.

FIG. 14 illustrates a lancet tip showing features, which can affectlancing pain, blood volume, and success rate.

FIG. 15 illustrates an embodiment of a lancet tip.

FIG. 16 is a graph showing displacement of a lancet over time.

FIG. 17 is a graph showing an embodiment of a velocity profile, whichincludes the velocity of a lancet over time including reduced velocityduring retraction of the lancet.

FIG. 18 illustrates the tip of an embodiment of a lancet before, duringand after the creation of an incision braced with a helix.

FIG. 19 illustrates a finger wound tract braced with an elastomerembodiment.

FIG. 20 is a perspective view of a tissue penetration device havingfeatures of the invention.

FIG. 21 is an elevation view in partial longitudinal section of thetissue penetration device of FIG. 20.

FIG. 22 is an elevation view in partial section of an alternativeembodiment.

FIG. 23 is a transverse cross sectional view of the tissue penetrationdevice of FIG. 21 taken along lines 23-23 of FIG. 21.

FIG. 24 is a transverse cross sectional view of the tissue penetrationdevice of FIG. 21 taken along lines 24-24 of FIG. 21.

FIG. 25 is a transverse cross sectional view of the tissue penetrationdevice of FIG. 21 taken along lines 25-25 of FIG. 21.

FIG. 26 is a transverse cross sectional view of the tissue penetrationdevice of FIG. 21 taken along lines 26-26 of FIG. 21.

FIG. 27 is a side view of the drive coupler of the tissue penetrationdevice of FIG. 21.

FIG. 28 is a front view of the drive coupler of the tissue penetrationdevice of FIG. 21 with the lancet not shown for purposes ofillustration.

FIGS. 29A-29C show a flowchart illustrating a lancet control method.

FIG. 30 is a diagrammatic view of a patient's finger and a lancet tipmoving toward the skin of the finger.

FIG. 31 is a diagrammatic view of a patient's finger and the lancet tipmaking contact with the skin of a patient's finger.

FIG. 32 is a diagrammatic view of the lancet tip depressing the skin ofa patient's finger.

FIG. 33 is a diagrammatic view of the lancet tip further depressing theskin of a patient's finger.

FIG. 34 is a diagrammatic view of the lancet tip penetrating the skin ofa patient's finger.

FIG. 35 is a diagrammatic view of the lancet tip penetrating the skin ofa patient's finger to a desired depth.

FIG. 36 is a diagrammatic view of the lancet tip withdrawing from theskin of a patient's finger.

FIGS. 37-41 illustrate a method of tissue penetration that may measureelastic recoil of the skin.

FIG. 42 is a graphical representation of position and velocity vs. timefor a lancing cycle.

FIG. 43 illustrates a sectional view of the layers of skin with a lancetdisposed therein.

FIG. 44 is a graphical representation of velocity vs. position of alancing cycle.

FIG. 45 is a graphical representation of velocity vs. time of a lancingcycle.

FIG. 46 is an elevation view in partial longitudinal section of analternative embodiment of a driver coil pack and position sensor.

FIG. 47 is a perspective view of a flat coil driver having features ofthe invention.

FIG. 48 is an exploded view of the flat coil driver of FIG. 47.

FIG. 49 is an elevational view in partial longitudinal section of atapered driver coil pack having features of the invention.

FIG. 50 is a transverse cross sectional view of the tapered coil driverpack of FIG. 49 taken along lines 50-50 in FIG. 49.

FIG. 51 shows an embodiment of a sampling module which houses a lancetand sample reservoir.

FIG; 52 shows a housing that includes a driver and a chamber where themodule shown in FIG. 51 can be loaded.

FIG. 53 shows a tissue penetrating sampling device with the moduleloaded into the housing.

FIG. 54 shows an alternate embodiment of a lancet configuration.

FIG. 55 illustrates an embodiment of a sample input port, samplereservoir and ergonomically contoured finger contact area.

FIG. 56 illustrates the tissue penetration sampling device during alancing event.

FIG. 57 illustrates a thermal sample sensor having a sample detectionelement near a surface over which a fluid may flow and an alternativeposition for a sampled detection element that would be exposed to afluid flowing across the surface.

FIG. 58 shows a configuration of a thermal sample sensor with a sampledetection element that includes a separate heating element.

FIG. 59 depicts three thermal sample detectors such as that shown inFIG. 58 with sample detection elements located near each other alongsidea surface.

FIG. 60 illustrates thermal sample sensors positioned relative to achannel having an analysis site.

FIG. 61 shows thermal sample sensors with sample detection analyzerspositioned relative to analysis sites arranged in an array on a surface.

FIG. 62 schematically illustrates a sampling module device includingseveral possible configurations of thermal sample sensors includingsample detection elements positioned relative to sample flow channelsand analytical regions.

FIG. 63 illustrates a tissue penetration sampling device having featuresof the invention.

FIG. 64 is a top view in partial section of a sampling module of thetissue penetration sampling device of FIG. 63.

FIG. 65 is a cross sectional view through line 65-65 of the samplingmodule shown in FIG. 64.

FIG. 66 schematically depicts a sectional view of an alternativeembodiment of the sampling module.

FIG. 67 depicts a portion of the sampling module surrounding a samplingport.

FIGS. 68-70 show in sectional view one implementation of a springpowered lancet driver in three different positions during use of thelancet driver.

FIG. 71 illustrates an embodiment of a tissue penetration samplingdevice having features of the invention.

FIG. 72 shows a top surface of a cartridge that includes multiplesampling modules.

FIG. 73 shows in partial section a sampling module of the samplingcartridge positioned in a reader device.

FIG. 74 is a perspective view in partial section of a tissue penetrationsampling device with a cartridge of sampling modules.

FIG. 75 is a front view in partial section of the tissue penetrationsampling device of FIG. 56.

FIG. 76 is a top view of the tissue penetration sampling device of FIG.75.

FIG. 77 is a perspective view of a section of a sampling module belthaving a plurality of sampling modules connected in series by a sheet offlexible polymer.

FIG. 78 is a perspective view of a single sampling module of thesampling module belt of FIG. 59.

FIG. 79 is a bottom view of a section of the flexible polymer sheet ofthe sampling module of FIG. 78 illustrating the flexible conductors andcontact points deposited on the bottom surface of the flexible polymersheet.

FIG. 80 is a perspective view of the body portion of the sampling moduleof FIG. 77 without the flexible polymer cover sheet or lancet.

FIG. 81 is an enlarged portion of the body portion of the samplingmodule of FIG. 80 illustrating the input port, sample flow channel,analytical region, lancet channel and lancet guides of the samplingmodule.

FIG. 82 is an enlarged elevational view of a portion of an alternativeembodiment of a sampling module having a plurality of small volumeanalytical regions.

FIG. 83 is a perspective view of a body portion of a lancet module thatcan house and guide a lancet without sampling or analytical functions.

FIG. 84 is an elevational view of a drive coupler having a T-slotconfigured to accept a drive head of a lancet.

FIG. 85 is an elevational view of the drive coupler of FIG. 84 from theside and illustrating the guide ramps of the drive coupler.

FIG. 86 is a perspective view of the drive coupler of FIG. 84 with alancet being loaded into the T-slot of the drive coupler.

FIG. 87 is a perspective view of the drive coupler of FIG. 86 with thedrive head of the lancet completely loaded into the T-slot of the drivecoupler.

FIG. 88 is a perspective view of a sampling module belt disposed withinthe T-slot of the drive coupler with a drive head of a lancet of one ofthe sampling modules loaded within the T-slot of the drive coupler.

FIG. 89 is a perspective view of a sampling module cartridge with thesampling modules arranged in a ring configuration.

FIG. 90 is a perspective view of a sampling module cartridge with theplurality of sampling modules arranged in a block matrix with lancetdrive heads configured to mate with a drive coupler having adhesivecoupling.

FIG. 91 is a side view of an alternative embodiment of a drive couplerhaving a lateral slot configured to accept the L-shaped drive head ofthe lancet that is disposed within a lancet module and shown with theL-shaped drive head loaded in the lateral slot.

FIG. 92 is an exploded view of the drive coupler, lancet with L-shapeddrive head and lancet module of FIG. 91.

FIG. 93 is a perspective view of the front of a lancet cartridge coupledto the distal end of a controlled electromagnetic driver.

FIG. 94 is an elevational front view of the lancet cartridge of FIG. 93.

FIG. 95 is a top view of the lancet cartridge of FIG. 93.

FIG. 96 is a perspective view of the lancet cartridge of FIG. 93 with aportion of the cartridge body and lancet receptacle not shown forpurposes of illustration of the internal mechanism.

FIGS. 97-101 illustrate an embodiment of an agent injection device.

FIGS. 102-106 illustrate an embodiment of a cartridge for use insampling having a sampling cartridge body and a lancet cartridge body.

DETAILED DESCRIPTION

Variations in skin thickness including the stratum corneum and hydrationof the epidermis can yield different results between different userswith existing tissue penetration devices, such as lancing deviceswherein the tissue penetrating element of the tissue penetration deviceis a lancet. Many current devices rely on adjustable mechanical stops ordamping, to control the lancet's depth of penetration.

Displacement velocity profiles for both spring driven and cam driventissue penetration devices are shown in FIGS. 1 and 2, respectively.Velocity is plotted against displacement X of the lancet. FIG. 1represents a displacement/velocity profile typical of spring drivendevices. The lancet exit velocity increases until the lancet hits thesurface of the skin 10. Because of the tensile characteristics of theskin, it will bend or deform until the lancet tip cuts the surface 20,the lancet will then penetrate the skin until it reaches a full stop 30.At this point displacement is maximal and reaches a limit of penetrationand the lancet stops. Mechanical stops absorb excess energy from the.driver and transfer it to the lancet. The energy stored in the springcan cause recoil resulting in multiple piercing as seen by the coiledprofile in FIG. 1. This results in unnecessary pain from the additionaltissue penetration as well as from transferring vibratory energy intothe skin and exciting nerve endings. Retraction of the lancet thenoccurs and the lancet exits the skin 40 to return into the housing.Velocity cannot be controlled in any meaningful way for this type ofspring-powered driver.

FIG. 2 shows a displacement/velocity profile for a cam driven driver,which is similar to that of FIG. 1, but because the return path isspecified in the cam configuration, there is no possibility of multipletissue penetrations from one actuation. Cam based drivers can offer somelevel of control of lancet velocity vs. displacement, but not enough toachieve many desirable displacement/velocity profiles.

Advantages are achieved by utilizing a controllable force driver todrive a lancet, such as a driver, powered by electromagnetic energy. Acontrollable driver can achieve a desired velocity versus positionprofile, such as that shown in FIG. 3. Embodiments of the presentinvention allow for the ability to accurately control depth ofpenetration, to control lancet penetration and withdrawal velocity, andtherefore reduce the pain perceived when cutting into the skin.Embodiments of the invention include a controllable driver that can beused with a feedback loop with a position sensor to control the powerdelivered to the lancet, which can optimize the velocity anddisplacement profile to compensate for variations in skin thickness

Pain reduction can be achieved by using a rapid lancet cutting speed,which is facilitated by the use of a lightweight lancet. The rapidcutting minimizes the shock waves produced when the lancet strikes theskin in addition to compressing the skin for efficient cutting. If acontrollable driver is used, the need for a mechanical stop can beeliminated. Due to the very light mass of the lancet and lack of amechanical stop, there is little or no vibrational energy transferred tothe finger during cutting.

The lancing devices such as those whose velocity versus positionprofiles are shown in FIGS. 1 and 2 typically yield 50% spontaneousblood. In addition, some lancing events are unsuccessful and yield noblood, even on milking the finger. A spontaneous blood dropletgeneration is dependent on reaching the blood capillaries and venuoles,which yield the blood sample. It is therefore an issue of correct depthof penetration of the cutting device. Due to variations in skinthickness and hydration, some types of skin will deform more beforecutting starts, and hence the actual depth of penetration will be less,resulting in less capillaries and venuoles cut. A controllable forcedriver can control the depth of penetration of a lancet and henceimprove the spontaneity of blood yield. Furthermore, the use of acontrollable force driver can allow for slow retraction of the lancet(slower than the cutting velocity) resulting in improved success ratedue to the would channel remaining open for the free passage of blood tothe surface of the skin.

Spontaneous blood yield occurs when blood from the cut vessels flow upthe wound tract to the surface of the skin, where it can be collectedand tested. Tissue elasticity parameters may force the wound tract toclose behind the retracting lancet preventing the blood from reachingthe surface. If however, the lancet were to be withdrawn slowly from thewound tract, thus keeping the wound open, blood could flow up the patentchannel behind the tip of the lancet as it is being withdrawn (ref.FIGS. 10 and 11). Hence the ability to control the lancet speed into andout of the wound allows the device to compensate for changes in skinthickness and variations in skin hydration and thereby achievesspontaneous blood yield with maximum success rate while minimizing pain.

An electromagnetic driver can be coupled directly to the lancetminimizing the mass of the lancet and allowing the driver to bring thelancet to a stop at a predetermined depth without the use of amechanical stop. Alternatively, if a mechanical stop is required forpositive positioning, the energy transferred to the stop can beminimized. The electromagnetic driver allows programmable control overthe velocity vs. position profile of the entire lancing processincluding timing the start of the lancet, tracking the lancet position,measuring the lancet velocity, controlling the distal stop acceleration,and controlling the skin penetration depth.

Referring to FIG. 4, an embodiment of a tissue penetration device isshown. The tissue penetration device includes a controllable forcedriver in the form of an electromagnetic driver, which can be used todrive a lancet. The term Lancet, as used herein, generally includes anysharp or blunt member, preferably having a relatively low mass, used topuncture the skin for the purpose of cutting blood vessels and allowingblood to flow to the surface of the skin. The term Electromagneticdriver, as used herein, generally includes any device that moves ordrives a tissue penetrating element, such as a lancet under anelectrically or magnetically induced force. FIG. 4 is a partiallyexploded view of an embodiment of an electromagnetic driver. The tophalf of the driver is shown assembled. The bottom half of the driver isshown exploded for illustrative purposes.

FIG. 4 shows the inner insulating housing 22 separated from thestationary housing or PC board 20, and the lancet 24 and flag 26assembly separated from the inner insulating housing 22 for illustrativepurposes. In addition, only four rivets 18 are shown as attached to theinner insulating housing 22 and separated from the PC board 20. In anembodiment, each coil drive field core in the PC board located in the PCBoard 20 and 30 is connected to the inner insulating housing 22 and 32with rivets.

The electromagnetic driver has a moving part comprising a lancetassembly with a lancet 24 and a magnetically permeable flag 26 attachedat the proximal or drive end and a stationary part comprising astationary housing assembly with electric field coils arranged so thatthey produce a balanced field at the flag to reduce or eliminate any netlateral force on the flag. The electric field coils are generally one ormore metal coils, which generate a magnetic field when electric currentpasses through the coil. The iron flag is a flat or enlarged piece ofmagnetic material, which increases the surface area of the lancetassembly to enhance the magnetic forces generated between the proximalend of the lancet and a magnetic field produced by the field coils. Thecombined mass of the lancet and the iron flag can be minimized tofacilitate rapid acceleration for introduction into the skin of apatient, to reduce the impact when the lancet stops in the skin, and tofacilitate prompt velocity profile changes throughout the samplingcycle.

The stationary housing assembly consists of a PC board 20, a lower innerinsulating housing 22, an upper inner insulating housing 32, an upper PCboard 30, and rivets 18 assembled into a single unit. The lower andupper inner insulating housing 22 and 32 are relieved to form a slot sothat lancet assembly can be slid into the driver assembly from the sideperpendicular to the direction of the lancet's advancement and.retraction. This allows the disposal of the lancet assembly and reuse ofthe stationary housing assembly with another lancet assembly whileavoiding accidental lancet launches during replacement.

The electric field coils in the upper and lower stationary housing 20and 30 are fabricated in a multi-layer printed circuit (PC) board. Theymay also be conventionally wound wire coils. A Teflon® material, orother low friction insulating material is used to construct the lowerand upper inner insulating housing 22 and 32. Each insulating housing ismounted on the PC board to provide electrical insulation and physicalprotection, as well as to provide a low-friction guide for the lancet.The lower and upper inner insulating housing 22 and 32 provide areference surface with a small gap so that the lancet assembly 24 and 26can align with the drive field coils in the PC board for good magneticcoupling.

Rivets 18 connect the lower inner insulating housing 22 to the lowerstationary housing 20 and are made of magnetically permeable materialsuch as ferrite or steel, which serves to concentrate the magneticfield. This mirrors the construction of the upper inner insulatinghousing 32 and upper stationary housing 30. These rivets form the polesof the electric field coils. The PC board is fabricated with multiplelayers of coils or with multiple boards. Each layer supports spiraltraces around a central hole. Alternate layers spiral from the centeroutwards or from the edges inward. In this way each layer connects viasimple feed-through holes, and the current always travels in the samedirection, summing the ampere-turns.

The PC boards within the lower and upper stationary housings 20 and 30are connected to the lower and upper inner insulating housings 22 and 32with the rivets 18. The lower and upper inner insulating housings 22 and32 expose the rivet heads on opposite ends of the slot where the lancetassembly 24 and 26 travels. The magnetic field lines from each rivetcreate magnetic poles at the rivet heads. An iron bar on the oppositeside of the PC board within each of the lower and upper stationaryhousing 20 and 30 completes the magnetic circuit by connecting therivets. Any fastener made of magnetically permeable material such asiron or steel can be used In place of the rivets. A single componentmade of magnetically permeable material and formed in a horseshoe shapecan be used in place of the rivet/screw and iron bar assembly. Inoperation, the magnetically permeable flag 26 attached to the lancet 24is divided into slits and bars 34. The slit patterns are staggered sothat coils can drive the flag 26 in two, three or more phases.

Both lower and upper PC boards 20 and 30 contain drive coils so thatthere is a symmetrical magnetic field above and below the flag 26. Whenthe pair of PC boards is turned on, a magnetic field is establishedaround the bars between the slits of the magnetically permeable iron onthe flag 26. The bars of the flag experience a force that tends to movethe magnetically permeable material to a position minimizing the numberand length of magnetic field lines and conducting the magnetic fieldlines between the magnetic poles.

When a bar of the flag 26 is centered between the rivets 18 of amagnetic pole, there is no net force on the flag, and any disturbingforce is resisted by imbalance in the field. This embodiment of thedevice operates on a principle similar to that of a solenoid. Solenoidscannot push by repelling iron; they can only pull by attracting the ironinto a minimum energy position. The slits 34 on one side of the flag 26are offset with respect to the other side by approximately one half ofthe pitch of the poles. By alternately activating the coils on each sideof the PC board, the lancet assembly can be moved with respect to thestationary housing assembly. The direction of travel is established byselectively energizing the coils adjacent the metal flag on the lancetassembly. Alternatively, a three phase, three-pole design or a shadingcoil that is offset by one-quarter pitch establishes the direction oftravel. The lower and upper PC boards 20 and 30 shown in FIG. 4 containelectric field coils, which drive the lancet assembly and the circuitryfor controlling the entire electromagnetic driver.

The embodiment described above generally uses the principles of amagnetic attraction drive, similar to commonly available circularstepper motors (Hurst Manufacturing BA Series motor, or “ElectricalEngineering Handbook” Second edition p 1472-1474, 1997). Thesereferences are hereby incorporated by reference. Other embodiments caninclude a linear induction drive that uses a changing magnetic field toinduce electric currents in the lancet assembly. These induced currentsproduce a secondary magnetic field that repels the primary field andapplies a net force on the lancet assembly. The linear induction driveuses an electrical drive control that sweeps a magnetic field from poleto pole, propelling the lancet before it. Varying the rate of the sweepand the magnitude of the field by altering the driving voltage andfrequency controls the force applied to the lancet assembly and itsvelocity.

The arrangement of the coils and rivets to concentrate the magnetic fluxalso applies to the induction design creating a growing magnetic fieldas the electric current in the field switches on. This growing magneticfield creates an opposing electric current in the conductive flag. In alinear induction motor the flag is electrically conductive, and itsmagnetic properties are unimportant. Copper or aluminum are materialsthat can be used for the conductive flags. Copper is generally usedbecause of its good electrical conductivity. The opposing electricalfield produces an opposing magnetic field that repels the field of thecoils. By phasing the power of the coils, a moving field can begenerated which pushes the flag along just below the synchronous speedof the coils. By controlling the rate of sweep, and by generatingmultiple sweeps, the flag can be moved at a desired speed.

FIG. 5 shows another embodiment of a solenoid type electromagneticdriver that is capable of driving an iron core or slug mounted to thelancet assembly using a direct current (DC) power supply. Theelectromagnetic driver includes a driver coil pack that is divided intothree separate coils along the path of the lancet, two end coils and amiddle coil. Direct current is alternated to the coils to advance andretract the lancet. Although the driver coil pack is shown with threecoils, any suitable number of coils may be used, for example, 4, 5, 6, 7or more coils may be used.

The stationary iron housing 40 contains the driver coil pack with afirst coil 52 is flanked by iron spacers 50 which concentrate themagnetic flux at the inner diameter creating magnetic poles. The innerinsulating housing 48 isolates the lancet 42 and iron core 46 from thecoils and provides a smooth, low friction guide surface. The lancetguide 44 further centers the lancet 42 and iron core 46. The lancet 42is protracted and retracted by alternating the current between the firstcoil 52, the middle coil, and the third coil to attract the iron core46. Reversing the coil sequence and attracting the core and lancet backinto the housing retracts the lancet. The lancet guide 44 also serves asa stop for the iron core 46 mounted to the lancet 42.

As discussed above, tissue penetration devices which employ spring orcam driving methods have a symmetrical or nearly symmetrical actuationdisplacement and velocity profiles on the advancement and retraction ofthe lancet as shown in FIGS. 6 and 7. In most of the available lancetdevices, once the launch is initiated, the stored energy determines thevelocity profile until the energy is dissipated. Controlling impact,retraction velocity, and dwell time of the lancet within the tissue canbe useful in order to achieve a high success rate while accommodatingvariations in skin properties and minimize pain. Advantages can beachieved by taking into account that tissue dwell time is related to theamount of skin deformation as the lancet tries to puncture the surfaceof the skin and variance in skin deformation from patient to patientbased on skin hydration.

The ability to control velocity and depth of penetration can be achievedby use of a controllable force driver where feedback is an integral partof driver control. Such drivers can control either metal or polymericlancets or any other type of tissue penetration element. The dynamiccontrol of such a driver is illustrated in FIG. 8 which illustrates anembodiment of a controlled displacement profile and FIG. 9 whichillustrates an embodiment of a the controlled velocity profile. Theseare compared to FIGS. 6 and 7, which illustrate embodiments ofdisplacement and velocity profiles, respectively, of a harmonicspring/mass powered driver.

Reduced pain can be achieved by using impact velocities of greater than2 m/s entry of a tissue penetrating element, such as a lancet, intotissue.

Retraction of the lancet at a low velocity following the sectioning ofthe venuole/capillary mesh allows the blood to flood the wound tract andflow freely to the surface, thus using the lancet to keep the channelopen during retraction as shown in FIGS. 10 and 11. Low-velocityretraction of the lancet near the wound flap prevents the wound flapfrom sealing off the channel. Thus, the ability to slow the lancetretraction directly contributes to increasing the success rate ofobtaining blood. Increasing the sampling success rate to near 100% canbe important to the combination of sampling and acquisition into anintegrated sampling module such as an integrated glucose-samplingmodule, which incorporates a glucose test strip.

Referring again to FIG. 5, the lancet and lancet driver are configuredso that feedback control is based on lancet displacement, velocity, oracceleration. The feedback control information relating to the actuallancet path is returned to a processor such as that illustrated in FIG.12 that regulates the energy to the driver, thereby preciselycontrolling the lancet throughout its advancement and retraction. Thedriver may be driven by electric current, which includes direct currentand alternating current.

In FIG. 5, the electromagnetic driver shown is capable of driving aniron core or slug mounted to the lancet assembly using a direct current(DC) power supply and is also capable of determining the position of theiron core by measuring magnetic coupling between the core and the coils.The coils can be used in pairs to draw the iron core into the drivercoil pack. As one of the coils is switched on, the corresponding inducedcurrent in the adjacent coil can be monitored. The strength of thisinduced current is related to the degree of magnetic coupling providedby the iron core, and can be used to infer the position of the core andhence, the relative position of the lancet.

After a period of time, the drive voltage can be turned off, allowingthe coils to relax, and then the cycle is repeated. The degree ofmagnetic coupling between the coils is converted electronically to aproportional DC voltage that is supplied to an analog-to-digitalconverter. The digitized position signal is then processed and comparedto a desired “nominal” position by a central processing unit (CPU). TheCPU to set the level and/or length of the next power pulse to thesolenoid coils uses error between the actual and nominal positions.

In another embodiment, the driver coil pack has three coils consistingof a central driving coil flanked by balanced detection coils built intothe driver assembly so that they surround an actuation or magneticallyactive region with the region centered on the middle coil at mid-stroke.When a current pulse is applied to the central coil, voltages areinduced in the adjacent sense coils. If the sense coils are connectedtogether so that their induced voltages oppose each other, the resultingsignal will be positive for deflection from mid-stroke in one direction,negative in the other direction, and zero at mid-stroke. This measuringtechnique is commonly used in Linear Variable Differential Transformers(LVDT). Lancet position is determined by measuring the electricalbalance between the two sensing coils.

In another embodiment, a feedback loop can use a commercially availableLED/photo transducer module such as the OPB703 manufactured by OptekTechnology, Inc., 1215 W. Crosby Road, Carrollton, Tex., 75006 todetermine the distance from the fixed module on the stationary housingto a reflective surface or target mounted on the lancet assembly. TheLED acts as a light emitter to send light beams to the reflectivesurface, which in turn reflects the light back to the photo transducer,which acts as a light sensor. Distances over the range of 4 mm or so aredetermined by measuring the intensity of the reflected light by thephoto transducer. In another embodiment, a feedback loop can use amagnetically permeable region on the lancet shaft itself as the core ofa Linear Variable Differential Transformer (LVDT).

A permeable region created by selectively annealing a portion of thelancet shaft, or by including a component in the lancet assembly, suchas ferrite, with sufficient magnetic permeability to allow couplingbetween adjacent sensing coils. Coil size, number of windings, drivecurrent, signal amplification, and air gap to the permeable region arespecified in the design process. In another embodiment, the feedback.control supplies a piezoelectric driver, superimposing a high frequencyoscillation on the basic displacement profile. The piezoelectric driverprovides improved cutting efficiency and reduces pain by allowing thelancet to “saw” its way into the tissue or to destroy cells withcavitation energy generated by the high frequency of vibration of theadvancing edge of the lancet. The drive power to the piezoelectricdriver is monitored for an impedance shift as the device interacts withthe target tissue. The resulting force measurement, coupled with theknown mass of the lancet is used to determine lancet acceleration,velocity, and position.

FIG. 12 illustrates the operation of a feedback loop using a processor.The processor 60 stores profiles 62 in non-volatile memory. A userinputs information 64 about the desired circumstances or parameters fora lancing event. The processor 60 selects a driver profile 62 from a setof alternative driver profiles that have been preprogrammed in theprocessor 60 based on typical or desired tissue penetration deviceperformance determined through testing at the factory or as programmedin by the operator. The processor 60 may customize by either scaling ormodifying the profile based on additional user input information 64.Once the processor has chosen and customized the profile, the processor60 is ready to modulate the power from the power supply 66 to the lancetdriver 68 through an amplifier 70. The processor 60 measures thelocation of the lancet 72 using a position sensing mechanism 74 throughan analog to digital converter 76. Examples of position sensingmechanisms have been described in the embodiments above. The processor60 calculates the movement of the lancet by comparing the actual profileof the lancet to the predetermined profile. The processor 60 modulatesthe power to the lancet driver 68 through a signal generator 78, whichcontrols the amplifier 70 so that the actual profile of the lancet doesnot exceed the predetermined profile by more than a preset error limit.The error limit is the accuracy in the control of the lancet.

After the lancing event, the processor 60 can allow the user to rank theresults of the lancing event. The processor 60 stores these results andconstructs a database 80 for the individual user. Using the database 80,the processor 60 calculates the profile traits such as degree ofpainlessness, success rate, and blood volume for various profiles 62depending on user input information 64 to optimize the profile to theindividual user for subsequent lancing cycles. These profile traitsdepend on the characteristic phases of lancet advancement andretraction. The processor 60 uses these calculations to optimizeprofiles 62 for each user. In addition to user input information 64, aninternal clock allows storage in the database 80 of information such asthe time of day to generate a time stamp for the lancing event and thetime between lancing events to anticipate the user's diurnal needs. Thedatabase stores information and statistics for each user and eachprofile that particular user uses.

In addition to varying the profiles, the processor 60 can be used tocalculate the appropriate lancet diameter and geometry necessary torealize the blood volume required by the user. For example, if the userrequires a 1-5 micro liter volume of blood, the processor selects a 200micron diameter lancet to achieve these results. For each class oflancet, both diameter and lancet tip geometry, is stored in theprocessor to correspond with upper and lower limits of attainable bloodvolume based on the predetermined displacement and velocity profiles.

The lancing device is capable of prompting the user for information atthe beginning and the end of the lancing event to more adequately suitthe user. The goal is to either change to a different profile or modifyan existing profile. Once the profile is set, the force driving thelancet is varied during advancement and retraction to follow theprofile. The method of lancing using the lancing device comprisesselecting a profile, lancing according to the selected profile,determining lancing profile traits for each characteristic phase of thelancing cycle, and optimizing profile traits for subsequent lancingevents.

FIG. 13 shows an embodiment of the characteristic phases of lancetadvancement and retraction on a graph of force versus time illustratingthe force exerted by the lancet driver on the lancet to achieve thedesired displacement and velocity profile. The characteristic phases arethe lancet introduction phase A-C where the lancet is longitudinallyadvanced into the skin, the lancet rest phase D where the lancetterminates its longitudinal movement reaching its maximum depth andbecoming relatively stationary, and the lancet retraction phase E-Gwhere the lancet is longitudinally retracted out of the skin. Theduration of the lancet retraction phase E-G is longer than the durationof the lancet introduction phase A-C, which in turn is longer than theduration of the lancet rest phase D.

The introduction phase further comprises a lancet launch phase prior toA when the lancet is longitudinally moving through air toward the skin,a tissue contact phase at the beginning of A when the distal end of thelancet makes initial contact with the skin, a tissue deformation phase Awhen the skin bends depending on its elastic properties which arerelated to hydration and thickness, a tissue lancing phase whichcomprises when the lancet hits the inflection point on the skin andbegins to cut the skin B and the lancet continues cutting the skin C.The lancet rest phase D is the limit of the penetration of the lancetinto the skin. Pain is reduced by minimizing the duration of the lancetintroduction phase A-C so that there is a fast incision to a certainpenetration depth regardless of the duration of the deformation phase Aand inflection point cutting B which will vary from user to user.Success rate is increased by measuring the exact depth of penetrationfrom inflection point B to the limit of penetration in the lancet restphase D. This measurement allows the lancet to always, or at leastreliably, hit the capillary beds which are a known distance underneaththe surface of the skin.

The lancet retraction phase further comprises a primary retraction phaseE when the skin pushes the lancet out of the wound tract, a secondaryretraction phase F when the lancet starts to become dislodged and pullsin the opposite direction of the skin, and lancet exit phase G when thelancet becomes free of the skin. Primary retraction is the result ofexerting a decreasing force to pull the lancet out of the skin as thelancet pulls away from the finger. Secondary retraction is the result ofexerting a force in the opposite direction to dislodge the lancet.Control is necessary to keep the wound tract open as blood flows up thewound tract. Blood volume is increased by using a uniform velocity toretract the lancet during the lancet retraction phase E-G regardless ofthe force required for the primary retraction phase E or secondaryretraction phase F, either of which may vary from user to user dependingon the properties of the user's skin.

FIG. 14 shows a standard industry lancet for glucose testing which has athree-facet geometry. Taking a rod of diameter 114 and grinding 8degrees to the plane of the primary axis to create the primary facet 110produces the lancet 116. The secondary facets 112 are then created byrotating the shaft of the needle 15 degrees, and then rolling over 12degrees to the plane of the primary facet. Other possible geometry'srequire altering the lancet's production parameters such as shaftdiameter, angles, and translation distance.

FIG. 15 illustrates facet and tip geometry 120 and 122, diameter 124,and depth 126 which are significant factors in reducing pain, bloodvolume and success rate. It is known that additional cutting by thelancet is achieved by increasing the shear percentage or ratio of theprimary to secondary facets, which when combined with reducing thelancet's diameter reduces skin tear and penetration force and gives theperception of less pain. Overall success rate of blood yield, however,also depends on a variety of factors, including the existence of facets,facet geometry, and skin anatomy.

FIG. 16 shows another embodiment of displacement versus time profile ofa lancet for a controlled lancet retraction. FIG. 17 shows the velocityvs. time profile of the lancet for the controlled retraction of FIG. 16.The lancet driver controls lancet displacement and velocity at severalsteps in the lancing cycle, including when the lancet cuts the bloodvessels to allow blood to pool 130, and as the lancet retracts,regulating the retraction rate to allow the blood to flood the woundtract while keeping the wound flap from sealing the channel 132 topermit blood to exit the wound.

In addition to slow retraction of a tissue-penetrating element in orderto hold the wound open to allow blood to escape to the skin surface,other methods are contemplated. FIG. 18 shows the use of an embodimentof the invention, which includes a retractable coil on the lancet tip. Acoiled helix or tube 140 is attached externally to lancet 116 with thefreedom to slide such that when the lancet penetrates the skin 150, thehelix or tube 140 follows the trajectory of the lancet 116. The helixbegins the lancing cycle coiled around the facets and shaft of thelancet 144. As the lancet penetrates the skin, the helix braces thewound tract around the lancet 146. As the lancet retracts, the helixremains to brace open the wound tract, keeping the wound tract fromcollapsing and keeping the surface skin flap from closing 148. Thisallows blood 152 to pool and flow up the channel to the surface of theskin. The helix is then retracted as the lancet pulls the helix to thepoint where the helix is decompressed to the point where the diameter ofthe helix becomes less than the diameter of the wound tract and becomesdislodged from the skin.

The tube or helix 140 is made of wire or metal of the type commonly usedin angioplasty stents such as stainless steel, nickel titanium alloy orthe like. Alternatively the tube or helix 140 or a ring can be made of abiodegradable material, which braces the wound tract by becoming lodgedin the skin. Biodegradation is completed within seconds or minutes ofinsertion, allowing adequate time for blood to pool and flow up thewound tract. Biodegradation is activated by heat, moisture, or pH fromthe skin.

Alternatively, the wound could be held open by coating the lancet with apowder or other granular substance. The powder coats the wound tract andkeeps it open when the lancet is withdrawn. The powder or other granularsubstance can be a coarse bed of microspheres or capsules which hold thechannel open while allowing blood to flow through the porousinterstices.

In another embodiment the wound can be held open using a two-partneedle, the outer part in the shape of a “U” and the inner part fillingthe “U.” After creating the wound the inner needle is withdrawn leavingan open channel, rather like the plugs that are commonly used forwithdrawing sap from maple trees.

FIG. 19 shows a further embodiment of a method and device forfacilitating blood flow utilizing an elastomer to coat the wound. Thismethod uses an elastomer 154, such as silicon rubber, to coat or bracethe wound tract 156 by covering and stretching the surface of the finger158. The elastomer 154 is applied to the finger 158 prior to lancing.After a short delay, the lancet (not shown) then penetrates theelastomer 154 and the skin on the surface of the finger 158 as is seenin 160. Blood is allowed to pool and rise to the surface while theelastomer 154 braces the wound tract 156 as is seen in 162 and 164.Other known mechanisms for increasing the success rate of blood yieldafter lancing can include creating a vacuum, suctioning the wound,applying an adhesive strip, vibration while cutting, or initiating asecond lance if the first is unsuccessful.

FIG. 20 illustrates an embodiment of a tissue penetration device, morespecifically, a lancing device 180 that includes a controllable driver179 coupled to a tissue penetration element. The lancing device 180 hasa proximal end 181 and a distal end 182. At the distal end 182 is thetissue penetration element in the form of a lancet 183, which is coupledto an elongate coupler shaft 184 by a drive coupler 185. The elongatecoupler shaft 184 has a proximal end 186 and a distal end 187. A drivercoil pack 188 is disposed about the elongate coupler shaft 184 proximalof the lancet 183. A position sensor 191 is disposed about a proximalportion 192 of the elongate coupler shaft 184 and an electricalconductor 194 electrically couples a processor 193 to the positionsensor 191. The elongate coupler shaft 184 driven by the driver coilpack 188 controlled by the position sensor 191 and processor 193 formthe controllable driver, specifically, a controllable electromagneticdriver.

Referring to FIG. 21, the lancing device 180 can be seen in more detail,in partial longitudinal section. The lancet 183 has a proximal end 195and a distal end 196 with a sharpened point at the distal end 196 of thelancet 183 and a drive head 198 disposed at the proximal end 195 of thelancet 183. A lancet shaft 201 is disposed between the drive head 198and the sharpened point 197. The lancet shaft 201 may be comprised ofstainless steel, or any other suitable material or alloy and have atransverse dimension of about 0.1 to about 0.4 mm. The lancet shaft mayhave a length of about 3 mm to about 50 mm, specifically, about 15 mm toabout 20 mm. The drive head 198 of the lancet 183 is an enlarged portionhaving a transverse dimension greater than a transverse dimension of thelancet shaft 201 distal of the drive head 198. This configuration allowsthe drive head 198 to be mechanically captured by the drive coupler 185.The drive head 198 may have a transverse dimension of about 0.5 to about2 mm.

A magnetic member 202 is secured to the elongate coupler shaft 184proximal of the drive coupler 185 on a distal portion 203 of theelongate coupler shaft 184. The magnetic member 202 is a substantiallycylindrical piece of magnetic material having an axial lumen 204extending the length of the magnetic member 202. The magnetic member 202has an outer transverse dimension that allows the magnetic member 202 toslide easily within an axial lumen 205 of a low friction, possiblylubricious, polymer guide tube 205′ disposed within the driver coil pack188. The magnetic member 202 may have an outer transverse dimension ofabout 1.0 to about 5.0 mm, specifically, about 2.3 to about 2.5 mm. Themagnetic member 202 may have a length of about 3.0 to about 5.0 mm,specifically, about 4.7 to about 4.9 mm. The magnetic member 202 can bemade from a variety of magnetic materials including ferrous metals suchas ferrous steel, iron, ferrite, or the like. The magnetic member 202may be secured to the distal portion 203 of the elongate coupler shaft184 by a variety of methods including adhesive or epoxy bonding,welding, crimping or any other suitable method.

Proximal of the magnetic member 202, an optical encoder flag 206 issecured to the elongate coupler shaft 184. The optical encoder flag 206is configured to move within a slot 207 in the position sensor 191. Theslot 207 of the position sensor 191 is formed between a first bodyportion 208 and a second body portion 209 of the position sensor 191.The slot 207 may have separation width of about 1.5 to about 2.0 mm. Theoptical encoder flag 206 can have a length of about 14 to about 18 mm, awidth of about 3 to about 5 mm and a thickness of about 0.04 to about0.06 mm.

The optical encoder flag 206 interacts with various optical beamsgenerated by LEDs disposed on or in the position sensor body portions208 and 209 in a predetermined manner. The interaction of the opticalbeams generated by the LEDs of the position sensor 191 generates asignal that indicates the longitudinal position of the optical flag 206relative to the position sensor 191 with a substantially high degree ofresolution. The resolution of the position sensor 191 may be about 200to about 400 cycles per inch, specifically, about 350 to about 370cycles per inch. The position sensor 191 may have a speed response time(position/time resolution) of 0 to about 120,000 Hz, where one dark andlight stripe of the flag constitutes one Hertz, or cycle per second. Theposition of the optical encoder flag 206 relative to the magnetic member202, driver coil pack 188 and position sensor 191 is such that theoptical encoder 191 can provide precise positional information about thelancet 183 over the entire length of the lancet's power stroke.

An optical encoder that is suitable for the position sensor 191 is alinear optical incremental encoder, model HEDS 9200, manufactured byAgilent Technologies. The model HEDS 9200 may have a length of about 20to about 30 mm, a width of about 8 to about 12 mm, and a height of about9 to about 11 mm. Although the position sensor 191 illustrated is alinear optical incremental encoder, other suitable position sensorembodiments could be used, provided they posses the requisite positionalresolution and time response. The HEDS 9200 is a two channel devicewhere the channels are 90 degrees out of phase with each other. Thisresults in a resolution of four times the basic cycle of the flag. Thesequadrature outputs make it possible for the processor to determine thedirection of lancet travel. Other suitable position sensors includecapacitive encoders, analog reflective sensors, such as the reflectiveposition sensor discussed above, and the like.

A coupler shaft guide 211 is disposed towards the proximal end 181 ofthe lancing device 180. The guide 211 has a guide lumen 212 disposed inthe guide 211 to slidingly accept the proximal portion 192 of theelongate coupler shaft 184. The guide 211 keeps the elongate couplershaft 184 centered horizontally and vertically in the slot 202 of theoptical encoder 191.

The driver coil pack 188, position sensor 191 and coupler shaft guide211 are all secured to a base 213. The base 213 is longitudinallycoextensive with the driver coil pack 188, position sensor 191 andcoupler shaft guide 211. The base 213 can take the form of a rectangularpiece of metal or polymer, or may be a more elaborate housing withrecesses, which are configured to accept the various components of thelancing device 180.

As discussed above, the magnetic member 202 is configured to slidewithin an axial lumen 205 of the driver coil pack 188. The driver coilpack 188 includes a most distal first coil 214, a second coil 215, whichis axially disposed between the first coil 214 and a third coil 216, anda proximal-most fourth coil 217. Each of the first coil 214, second coil215, third coil 216 and fourth coil 217 has an axial lumen. The axiallumens of the first through fourth coils are configured to be coaxialwith the axial lumens of the other coils and together form the axiallumen 205 of the driver coil pack 188 as a whole. Axially adjacent eachof the coils 214-217 is a magnetic disk or washer 218 that augmentscompletion of the magnetic circuit of the coils 214-217 during a lancingcycle of the device 180. The magnetic washers 218 of the embodiment ofFIG. 21 are made of ferrous steel but could be made of any othersuitable magnetic material, such as iron or ferrite. The outer shell 189of the driver coil pack 188 is also made of iron or steel to completethe magnetic path around the coils and between the washers 218. Themagnetic washers 218 have an outer diameter commensurate with an outerdiameter of the driver coil pack 188 of about 4.0 to about 8.0 mm. Themagnetic washers 218 have an axial thickness of about 0.05, to about 0.4mm, specifically, about 0.15 to about 0.25 mm.

Wrapping or winding an elongate electrical conductor 221 about an axiallumen until a sufficient number of windings have been achieved forms thecoils 214-217. The elongate electrical conductor 221 is generally aninsulated solid copper wire with a small outer transverse dimension ofabout 0.06 mm to about 0.88 mm, specifically, about 0.3 mm to about 0.5mm. In one embodiment, 32 gauge copper wire is used for the coils214-217. The number of windings for each of the coils 214-217 of thedriver pack 188 may vary with the size of the coil, but for someembodiments each coil 214-217 may have about 30 to about 80 turns,specifically, about 50 to about 60 turns. Each coil 214-217 can have anaxial length of about 1.0 to about 3.0 mm, specifically, about 1.8 toabout 2.0 mm. Each coil 214-217 can have an outer transverse dimensionor diameter of about 4.0, to about 2.0 mm, specifically, about 9.0 toabout 12.0 mm. The axial lumen 205 can have a transverse dimension ofabout 1.0 to about 3.0 mm.

It may be advantageous in some driver coil 188 embodiments to replaceone or more of the coils with permanent magnets, which produce amagnetic field similar to that of the coils when the coils areactivated. In particular, it may be desirable in some embodiments toreplace the second coil 215, the third coil 216 or both with permanentmagnets. In addition, it may be advantageous to position a permanentmagnet at or near the proximal end of the coil driver pack in order toprovide fixed magnet zeroing function for the magnetic member (Adamsmagnetic Products 23A0002 flexible magnet material (800) 747-7543).

FIGS. 20 and 21 show a permanent bar magnet 219 disposed on the proximalend of the driver coil pack 188. As shown in FIG. 21, the bar magnet 219is arranged so as to have one end disposed adjacent the travel path ofthe magnetic member 202 and has a polarity configured so as to attractthe magnetic member 202 in a centered position with respect to the barmagnet 219. Note that the polymer guide tube 205′ can be configured toextend proximally to insulate the inward radial surface of the barmagnet 219 from an outer surface of the magnetic member 202. Thisarrangement allows the magnetic member 219 and thus the elongate couplershaft 184 to be attracted to and held in a zero point or rest positionwithout the consumption of electrical energy from the power supply 225.

Having a fixed zero or start point for the elongate coupler shaft 184and lancet 183 can be critical to properly controlling the depth ofpenetration of the lancet 183 as well as other lancing parameters. Thiscan be because some methods of depth penetration control for acontrollable driver measure the acceleration and displacement of theelongate coupler shaft 184 and lancet 183 from a known start position.If the distance of the lancet tip 196 from the target tissue is known,acceleration and displacement of the lancet is known and the startposition of the lancet is know, the time and position of tissue contactand depth of penetration can be determined by the processor 193.

Any number of configurations for a magnetic bar 219 can be used for thepurposes discussed above. In particular, a second permanent bar magnet(not shown) could be added to the proximal end of the driver coil pack188 with the magnetic fields of the two bar magnets configured tocomplement each other. In addition, a disc magnet 219′ could be used asillustrated in FIG. 22. Disc magnet 219′ is shown disposed at theproximal end of the driver coiled pack 188 with a polymer non-magneticdisc 219″ disposed between the proximal-most coil 217 and disc magnet219′ and positions disc magnet 219′ away from the proximal end of theproximal-most coil 217. The polymer non-magnetic disc spacer 219″ isused so that the magnetic member 202 can be centered in a zero or startposition slightly proximal of the proximal-most coil 217 of the drivercoil pack 188. This allows the magnetic member to be attracted by theproximal-most coil 217 at the initiation of the lancing cycle instead ofbeing passive in the forward drive portion of the lancing cycle.

An inner lumen of the polymer non-magnetic disc 219″ can be configuredto allow the magnetic member 202 to pass axially there through while aninner lumen of the disc magnet 219′ can be configured to allow theelongate coupler shaft 184 to pass through but not large enough for themagnetic member 202 to pass through. This results in the magnetic member202 being attracted to the disc magnet 219′ and coming to rest with theproximal surface of the magnetic member 202 against a distal surface ofthe disc magnet 219′. This arrangement provides for a positive andrepeatable stop for the magnetic member, and hence the lancet. A similarconfiguration could also be used for the bar magnet 219 discussed above.

Typically, when the electrical current in the coils 214-217 of thedriver coil pack 188 is off, a magnetic member 202 made of soft iron isattracted to the bar magnet 219 or disc magnet 219′. The magnetic fieldof the driver coil pack 188 and the bar magnet 219 or disc magnet 219′,or any other suitable magnet, can be configured such that when theelectrical current in the coils 214-217 is turned on, the leakagemagnetic field from the coils 214-217 has the same polarity as the barmagnet 219 or disc magnet 219′. This results in a magnetic force thatrepels the magnetic member 202 from the bar magnet 219 or disc magnet219′ and attracts the magnetic member 202 to the activated coils214-217. For this configuration, the bar magnet 219 or disc magnet thusact to facilitate acceleration of the magnetic member 202 as opposed toworking against the acceleration.

Electrical conductors 222 couple the driver coil pack 188 with theprocessor 193 which can be configured or programmed to control thecurrent flow in the coils 214-217 of the driver coil pack 188 based onposition feedback from the position sensor 191, which is coupled to theprocessor 193 by electrical conductors 194. A power source 225 iselectrically coupled to the processor 193 and provides electrical powerto operate the processor 193 and power the coil driver pack 188. Thepower source 225 may be one or more batteries that provide directcurrent power to the 193 processor.

FIG. 23 shows a transverse cross sectional view of drive coupler 185 inmore detail. The drive head 198 of the lancet 183 is disposed within thedrive coupler 185 with a first retaining rail 226 and second retainingrail 227 capturing the drive head 198 while allowing the drive head 198to be inserted laterally into the drive coupler 185 and retractedlaterally with minimal mechanical resistance. The drive coupler 185 mayoptionally be configured to include snap ridges 228 which allow thedrive head 198 to be laterally inserted and retracted, but keep thedrive head 198 from falling out of the drive coupler 185 unless apredetermined amount of externally applied lateral force is applied tothe drive head 198 of the lancet 183 towards the lateral opening 231 ofthe drive coupler 185. FIG. 27 shows an enlarged side view into thecoupler opening 231 of the drive coupler 185 showing the snap ridges 228disposed in the lateral opening 231 and the retaining rails 226 and 227.FIG. 28 shows an enlarged front view of the drive coupler 185. The drivecoupler 185 can be made from an alloy such as stainless steel, titaniumor aluminum, but may also be made from a suitable polymer such as ABS,PVC, polycarbonate plastic or the like. The drive coupler may be open onboth sides allowing the drive head and lancet to pass through.

Referring to FIG. 24, the magnetic member 202 is disposed about andsecured to the elongate coupler shaft 184. The magnetic member 202 isdisposed within the axial lumen 232 of the fourth coil 217. The drivercoil pack 188 is secured to the base 213. In FIG. 25 the position sensor191 is secured to the base 213 with the first body portion 208 of theposition sensor 191 disposed opposite the second body portion 209 of theposition sensor 191 with the first and second body portions 208 and 209of the position sensor 191 separated by the gap or slot 207. Theelongate coupler shaft 184 is slidably disposed within the gap 207between the first and second body portions 208 and 209 of the positionsensor 191. The optical encoder flag 206 is secured to the elongatecoupler shaft 184 and disposed between the first body portion 208 andsecond body portion 209 of the position sensor 191. Referring to FIG.26, the proximal portion 192 of the elongate coupler shaft 184 isdisposed within the guide lumen 212 of the coupler shaft guide 211. Theguide lumen 212 of the coupler shaft guide 211 may be lined with a lowfriction material such as Teflon® or the like to reduce friction of theelongate coupler shaft 184 during the power stroke of the lancing device180.

Referring to FIGS. 29A-29C, a flow diagram is shown that describes theoperations performed by the processor 193 in controlling the lancet 183of the lancing device 180 discussed above during an operating cycle.FIGS. 30-36 illustrate the interaction of the lancet 183 and skin 233 ofthe patient's finger 234 during an operation cycle of the lancet device183. The processor 193 operates under control of programming steps thatare stored in an associated memory. When the programming steps areexecuted, the processor 193 performs operations as described herein.Thus, the programming steps implement the functionality of theoperations described with respect to the flow diagram of FIG. 29. Theprocessor 193 can receive the programming steps from a program productstored in recordable media, including a direct access program productstorage device such as a hard drive or flash ROM, a removable programproduct storage device such as a floppy disk, or in any other mannerknown to those of skill in the art. The processor 193 can also downloadthe programming steps through a network connection or serial connection.

In the first operation, represented by the flow diagram box numbered 245in FIG. 29A, the processor 193 initializes values that it stores inmemory relating to control of the lancet, such as variables that it usesto keep track of the controllable driver 179 during movement. Forexample, the processor may set a clock value to zero and a lancetposition value to zero or to some other initial value. The processor 193may also cause power to be removed from the coil pack 188 for a periodof time, such as for about 10 ms, to allow any residual flux todissipate from the coils.

In the initialization operation, the processor 193 also causes thelancet to assume an initial stationary position. When in the initialstationary position, the lancet 183 is typically fully retracted suchthat the magnetic member 202 is positioned substantially adjacent thefourth coil 217 of the driver coil pack 188, shown in FIG. 21 above. Theprocessor 193 can move the lancet 183 to the initial stationary positionby pulsing an electrical current to the fourth coil 217 to therebyattract the magnetic member 202 on the lancet 183 to the fourth coil217. Alternatively, the magnetic member can be positioned in the initialstationary position by virtue of a permanent magnet, such as bar magnet219, disc magnet 219′ or any other suitable magnet as discussed abovewith regard to the tissue penetration device illustrated in FIGS. 20 and21.

In the next operation, represented by the flow diagram box numbered 247,the processor 193 energizes one or more of the coils in the coil pack188. This should cause the lancet 183 to begin to move (i.e., achieve anon-zero speed) toward the skin target 233. The processor 193 thendetermines whether or not the lancet is indeed moving, as represented bythe decision box numbered 249. The processor 193 can determine whetherthe lancet 183 is moving by monitoring the position of the lancet 183 todetermine whether the position changes over time. The processor 193 canmonitor the position of the lancet 183 by keeping track of the positionof the optical encoder flag 206 secured to the elongate coupler shaft184 wherein the encoder 191 produces a signal coupled to the processor193 that indicates the spatial position of the lancet 183.

If the processor 193 determines (via timeout without motion events) thatthe lancet 183 is not moving (a “No” result from the decision box 249),then the process proceeds to the operation represented by the flowdiagram box numbered 253, where the processor deems that an errorcondition is present. This means that some error in the system iscausing the lancet 183 not to move. The error may be mechanical,electrical, or software related. For example, the lancet 183 may bestuck in the stationary position because something is impeding itsmovement.

If the processor 193 determines that the lancet 183 is indeed moving (a“Yes” result from the decision box numbered 249), then the processproceeds to the operation represented by the flow diagram box numbered257. In this operation, the processor 193 causes the lancet 183 tocontinue to accelerate and launch toward the skin target 233, asindicated by the arrow 235 in FIG. 30. The processor 193 can achieveacceleration of the lancet 183 by sending an electrical current to anappropriate coil 214-217 such that the coil 214-217 exerts an attractivemagnetic launching force on the magnetic member 202 and causes themagnetic member 202 and the lancet 183 coupled thereto to move in adesired direction. For example, the processor 193 can cause anelectrical current to be sent to the third coil 216 so that the thirdcoil 216 attracts the magnetic member 202 and causes the magnetic member202 to move from a position adjacent the fourth coil 217 toward thethird coil 216. The processor preferably determines which coil 214-217should be used to attract the magnetic member 202 based on the positionof the magnetic member 202 relative to the coils 214-217. In thismanner, the processor 193 provides a controlled force to the lancet thatcontrols the movement of the lancet.

During this operation, the processor 193 periodically or continuallymonitors the position and/or velocity of the lancet 183. In keepingtrack of the velocity and position of the lancet 183 as the lancet 183moves towards the patient's skin 233 or other tissue, the processor 193also monitors and adjusts the electrical current to the coils 214-217.In some embodiments, the processor 193 applies current to an appropriatecoil 214-217 such that the lancet 183 continues to move according to adesired direction and acceleration. In the instant case, the processor193 applies current to the appropriate coil 214-217 that will cause thelancet 183 to continue to move in the direction of the patient's skin233 or other tissue to be penetrated.

The processor 193 may successively transition the current between coils214-217 so that as the magnetic member 202 moves past a particular coil214-217, the processor 193 then shuts off current to that coil 214-217and then applies current to another coil 214-217 that will attract themagnetic member 202 and cause the magnetic member 202 to continue tomove in the desired direction. In transitioning current between thecoils 214-217, the processor 193 can take into account various factors,including the speed of the lancet 183, the position of the lancet 183relative to the coils 214-217, the number of coils 214-217, and thelevel of current to be applied to the coils 214-217 to achieve a desiredspeed or acceleration.

In the next operation, the processor 193 determines whether the cuttingor distal end tip 196 of the lancet 183 has contacted the patient's skin233, as shown in FIG. 31 and as represented by the decision box numbered265 in FIG. 29B. The processor 193 may determine whether the lancet 183has made contact with the target tissue 233 by a variety of methods,including some that rely on parameters which are measured prior toinitiation of a lancing cycle and other methods that are adaptable touse during a lancing cycle without any predetermined parameters.

In one embodiment, the processor 193 determines that the skin has beencontacted when the end tip 196 of the lancet 183 has moved apredetermined distance with respect to its initial position. If thedistance from the tip 961 of the lancet 183 to the target tissue 233 isknown prior to initiation of lancet 183 movement, the initial positionof the lancet 183 is fixed and known, and the movement and position ofthe lancet 183 can be accurately measured during a lancing cycle, thenthe position and time of lancet contact can be determined.

This method requires an accurate measurement of the distance between thelancet tip 196 and the patient's skin 233 when the lancet 183 is in thezero time or initial position. This can be accomplished in a number ofways. One way is to control all of the mechanical parameters thatinfluence the distance from the lancet tip 196 to the patient's tissueor a surface of the lancing device 180 that will contact the patient'sskin 233. This could include the start position of the magnetic member202, magnetic path tolerance, magnetic member 202 dimensions, drivercoil pack 188 location within the lancing device 180 as a whole, lengthof the elongate coupling shaft 184, placement of the magnetic member 202on the elongate coupling shaft 184, length of the lancet 183 etc.

If all these parameters, as well as others can be suitably controlled inmanufacturing with a tolerance stack-up that is acceptable, then thedistance from the lancet tip 196 to the target tissue 233 can bedetermined at the time of manufacture of the lancing device 180. Thedistance could then be programmed into the memory of the processor 193.If an adjustable feature is added to the lancing device 180, such as anadjustable length elongate coupling shaft 184, this can accommodatevariations in all of the parameters noted above, except length of thelancet 183. An electronic alternative to this mechanical approach wouldbe to calibrate a stored memory contact point into the memory of theprocessor 193 during manufacture based on the mechanical parametersdescribed above.

In another embodiment, moving the lancet tip 196 to the target tissue233 very slowly and gently touching the skin 233 prior to actuation canaccomplish the distance from the lancet tip 196 to the tissue 233. Theposition sensor can accurately measure the distance from theinitialization point to the point of contact, where the resistance toadvancement of the lancet 183 stops the lancet movement. The lancet 183is then retracted to the initialization point having measured thedistance to the target tissue 233 without creating any discomfort to theuser.

In another embodiment, the processor 193 may use software to determinewhether the lancet 183 has made contact with the patient's skin 233 bymeasuring for a sudden reduction in velocity of the lancet 183 due tofriction or resistance imposed on the lancet 183 by the patient's skin233. The optical encoder 191 measures displacement of the lancet 183.The position output data provides input to the interrupt input of theprocessor 193. The processor 193 also has a timer capable of measuringthe time between interrupts. The distance between interrupts is knownfor the optical encoder 191, so the velocity of the lancet 183 can becalculated by dividing the distance between interrupts by the timebetween the interrupts.

This method requires that velocity losses to the lancet 183 and elongatecoupler 184 assembly due to friction are known to an acceptable level sothat these velocity losses and resulting deceleration can be accountedfor when establishing a deceleration threshold above which contactbetween lancet tip 196 and target tissue 233 will be presumed. This sameconcept can be implemented in many ways. For example, rather thanmonitoring the velocity of the lancet 183, if the processor 193 iscontrolling the lancet driver in order to maintain a fixed velocity, thepower to the driver 188 could be monitored. If an amount of power abovea predetermined threshold is required in order to maintain a constantvelocity, then contact between the tip of the lancet 196 and the skin233 could be presumed.

In yet another embodiment, the processor 193 determines skin 233 contactby the lancet 183 by detection of an acoustic signal produced by the tip196 of the lancet 183 as it strikes the patient's skin 233. Detection ofthe acoustic signal can be measured by an acoustic detector 236 placedin contact with the patient's skin 233 adjacent a lancet penetrationsite 237, as shown in FIG. 31. Suitable acoustic detectors 236 includepiezo electric transducers, microphones and the like. The acousticdetector 236 transmits an electrical signal generated by the acousticsignal to the processor 193 via electrical conductors 238. In anotherembodiment, contact of the lancet 183 with the patient's skin 233 can bedetermined by measurement of electrical continuity in a circuit thatincludes the lancet 183, the patient's finger 234 and an electricalcontact pad 240 that is disposed on the patient's skin 233 adjacent thecontact site 237 of the lancet 183, as shown in FIG. 31. In thisembodiment, as soon as the lancet 183 contacts the patient's skin 233,the circuit 239 is completed and current flows through the circuit 239.Completion of the circuit 239 can then be detected by the processor 193to confirm skin 233 contact by the lancet 183.

If the lancet 183 has not contacted the target skin 233, then theprocess proceeds to a timeout operation, as represented by the decisionbox numbered 267 in FIG. 29B. In the timeout operation, the processor193 waits a predetermined time period. If the timeout period has not yetelapsed (a “No” outcome from the decision box 267), then the processorcontinues to monitor whether the lancet has contacted the target skin233. The processor 193 preferably continues to monitor the position andspeed of the lancet 183, as well as the electrical current to theappropriate coil 214-217 to maintain the desired lancet 183 movement. Ifthe timeout period elapses without the lancet 183 contacting the skin (a“Yes” output from the decision box 267), then it is deemed that thelancet 183 Will not contact the skin and the process proceeds to awithdraw phase, where the lancet is withdrawn away from the skin 233, asdiscussed more fully below. The lancet 183 may not have contacted thetarget skin 233 for a variety of reasons, such as if the patient removedthe skin 233 from the lancing device or if something obstructed thelancet 183 prior to it contacting the skin.

The processor 193 may also proceed to the withdraw phase prior to skincontact for other reasons. For example, at some point after initiationof movement of the lancet 183, the processor 193 may determine that theforward acceleration of the lancet 183 towards the patient's skin 233should be stopped or that current to all coils 214-217 should be shutdown. This can occur, for example, if it is determined that the lancet183 has achieved sufficient forward velocity, but has not yet contactedthe skin 233. In one embodiment, the average penetration velocity of thelancet 183 from the point of contact with the skin to the point ofmaximum penetration may be about 2.0 to about 10.0 m/s, specifically,about 3.8 to about 4.2 m/s. In another embodiment, the averagepenetration velocity of the lancet, may be from about 2 to about 8meters per second, specifically, about 2 to about 4 m/s.

The processor 193 can also proceed to the withdraw phase if it isdetermined that the lancet 183 has fully extended to the end of thepower stroke of the operation cycle of lancing procedure. In otherwords, the process may proceed to withdraw phase when an axial center241 of the magnetic member 202 has moved distal of an axial center 242of the first coil 214 as show in FIG. 21. In this situation, anycontinued power to any of the coils 214-217 of the driver coil pack 188serves to decelerate the magnetic member 202 and thus the lancet 183. Inthis regard, the processor 193 considers the length of the lancet 183(which can be stored in memory) the position of the lancet 183 relativeto the magnetic member 202, as well as the distance that the lancet 183has traveled.

With reference again to the decision box 265 in FIG. 29B, if theprocessor 193 determines that the lancet 183 has contacted the skin 233(a “Yes” outcome from the decision box 265), then the processor 193 canadjust the speed of the lancet 183 or the power delivered to the lancet183 for skin penetration to overcome any frictional forces on the lancet183 in order to maintain a desired penetration velocity of the lancet.The flow diagram box numbered 267 represents this.

As the velocity of the lancet 183 is maintained after contact with theskin 233, the distal tip 196 of the lancet 183 will first begin todepress or tent the contacted skin 237 and the skin 233 adjacent thelancet 183 to form a tented portion 243 as shown in FIG. 32 and furthershown in FIG. 33. As the lancet 183 continues to move in a distaldirection or be driven in a distal direction against the patient's skin233, the lancet 183 will eventually begin to penetrate the skin 233, asshown in FIG. 34. Once penetration of the skin 233 begins, the staticforce at the distal tip 196 of the lancet 183 from the skin 233 willbecome a dynamic cutting force, which is generally less than the statictip force. As a result in the reduction of force on the distal tip 196of the lancet 183 upon initiation of cutting, the tented portion 243 ofthe skin 233 adjacent the distal tip 196 of the lancet 183 which hadbeen depressed as shown in FIGS. 32 and 24 will spring back as shown inFIG. 34.

In the next operation, represented by the decision box numbered 271 inFIG. 29B, the processor 193 determines whether the distal end 196 of thelancet 183 has reached a brake depth. The brake depth is the skinpenetration depth for which the processor 193 determines thatdeceleration of the lancet 183 is to be initiated in order to achieve adesired final penetration depth 244 of the lancet 183 as show in FIG.35. The brake depth may be pre-determined and programmed into theprocessor's memory, or the processor 193 may dynamically determine thebrake depth during the actuation. The amount of penetration of thelancet 183 in the skin 233 of the patient may be measured during theoperation cycle of the lancet device 180. In addition, as discussedabove, the penetration depth necessary for successfully obtaining auseable sample can depend on the amount of tenting of the skin 233during the lancing cycle. The amount of tenting of the patient's skin233 can in turn depend on the tissue characteristics of the patient suchas elasticity, hydration etc. A method for determining thesecharacteristics is discussed below with regard to skin 233 tentingmeasurements during the lancing cycle and illustrated in FIGS. 37-41.

Penetration measurement can be carried out by a variety of methods thatare not dependent on measurement of tenting of the patient's skin. Inone embodiment, the penetration depth of the lancet 183 in the patient'sskin 233 is measured by monitoring the amount of capacitance between thelancet 183 and the patient's skin 233. In this embodiment, a circuitincludes the lancet 183, the patient's finger 234, the processor 193 andelectrical conductors connecting these elements. As the lancet 183penetrates the patient's skin 233, the greater the amount ofpenetration, the greater the surface contact area between the lancet 183and the patient's skin 233. As the contact area increases, so does thecapacitance between the skin 233 and the lancet 183. The increasedcapacitance can be easily measured by the processor 193 using methodsknown in the art and penetration depth can then be correlated to theamount of capacitance. The same method can be used by measuring theelectrical resistance between the lancet 183 and the patient's skin.

If the brake depth has not yet been reached, then a “No” results fromthe decision box 271 and the process proceeds to the timeout operationrepresented by the flow diagram box numbered 273. In the timeoutoperation, the processor 193 waits a predetermined time period. If thetimeout period has not yet elapsed (a “No” outcome from the decision box273), then the processor continues to monitor whether the brake depthhas been reached. If the timeout period elapses without the lancet 183achieving the brake depth (a “Yes” output from the decision box 273),then the processor 193 deems that the lancet 183 will not reach thebrake depth and the process proceeds to the withdraw phase, which isdiscussed more fully below. This may occur, for example, if the lancet183 is stuck at a certain depth.

With reference again to the decision box numbered 271 in FIG. 29B, ifthe lancet does reach the brake depth (a “Yes” result), then the processproceeds to the operation represented by the flow diagram box numbered275. In this operation, the processor 193 causes a braking force to beapplied to the lancet to thereby reduce the speed of the lancet 183 toachieve a desired amount of final skin penetration depth 244, as shownin FIG. 26. Note that FIGS. 32 and 33 illustrate the lancet makingcontact with the patient's skin and deforming or depressing the skinprior to any substantial penetration of the skin. The speed of thelancet 183 is preferably reduced to a value below a desired thresholdand is ultimately reduced to zero. The processor 193 can reduce thespeed of the lancet 183 by causing a current to be sent to a 214-217coil that will exert an attractive braking force on the magnetic member202 in a proximal direction away from the patient's tissue or skin 233,as indicated by the arrow 290 in FIG. 36. Such a negative force reducesthe forward or distally oriented speed of the lancet 183. The processor193 can determine which coil 214-217 to energize based upon the positionof the magnetic member 202 with respect to the coils 214-217 of thedriver coil pack 188, as indicated by the position sensor 191.

In the next operation, the process proceeds to the withdraw phase, asrepresented by the flow diagram box numbered 277. The withdraw phasebegins with the operation represented by the flow diagram box numbered279 in FIG. 29C. Here, the processor 193 allows the lancet 183 to settleat a position of maximum skin penetration 244, as shown in FIG. 35. Inthis regard, the processor 193 waits until any motion in the lancet 183(due to vibration from impact and spring energy stored in the skin,etc.) has stopped by monitoring changes in position of the lancet 183.The processor 193 preferably waits until several milliseconds (ms), suchas on the order of about 8 ms, have passed with no changes in positionof the lancet 183. This is an indication that movement of the lancet 183has ceased entirely. In some embodiments, the lancet may be allowed tosettle for about 1 to about 2000 milliseconds, specifically, about 50 toabout 200 milliseconds. For other embodiments, the settling time may beabout 1 to about 200 milliseconds.

It is at this stage of the lancing cycle that a software method can beused to measure the amount of tenting of the patient's skin 233 and thusdetermine the skin 233 characteristics such as elasticity, hydration andothers. Referring to FIGS. 37-41, a lancet 183 is illustrated in variousphases of a lancing cycle with target tissue 233. FIG. 37 shows tip 196of lancet 183 making initial contact with the skin 233 at the point ofinitial impact.

FIG. 38 illustrates an enlarged view of the lancet 183 making initialcontact with the tissue 233 shown in FIG. 37. In FIG. 39, the lancet tip196 has depressed or tented the skin 233 prior to penetration over adistance of X, as indicated by the arrow labeled X in FIG. 39. In FIG.40, the lancet 183 has reached the full length of the cutting powerstroke and is at maximum displacement. In this position, the lancet tip196 has penetrated the tissue 233 a distance of Y, as indicated by thearrow labeled Y in FIG. 39. As can be seen from comparing FIG. 38 withFIG. 40, the lancet tip 196 was displaced a total distance of X plus Yfrom the time initial contact with the skin 233 was made to the time thelancet tip 196 reached its maximum extension as shown in FIG. 40.However, the lancet tip 196 has only penetrated the skin 233 a distanceY because of the tenting phenomenon.

At the end of the power stroke of the lancet 183, as discussed abovewith regard to FIG. 26 and box 279 of FIG. 29C, the processor 193 allowsthe lancet to settle for about 8 msec. It is during this settling timethat the skin 233 rebounds or relaxes back to approximately its originalconfiguration prior to contact by the lancet 183 as shown in FIG. 41.The lancet tip 196 is still buried in the skin to a depth of Y, as shownin FIG. 41, however the elastic recoil of the tissue has displaced thelancet rearward or retrograde to the point of inelastic tenting that isindicated by the arrows Z in FIG. 41. During the rearward displacementof the lancet 183 due to the elastic tenting of the tissue 233, theprocessor reads and stores the position data generated by the positionsensor 191 and thus measures the amount of elastic tenting, which is thedifference between X and Z.

The tenting process and retrograde motion of the lancet 183 during thelancing cycle is illustrated graphically in FIG. 42 which shows both avelocity versus time graph and a position versus time graph of a lancettip 196 during a lancing cycle that includes elastic and inelastictenting. In FIG. 42, from point 0 to point A, the lancet 183 is beingaccelerated from the initialization position or zero position. Frompoint A to point B, the lancet is in ballistic or coasting mode, with noadditional power being delivered. At point B, the lancet tip 196contacts the tissue 233 and begins to tent the skin 233 until it reachesa displacement C. As the lancet tip 196 approaches maximum displacement,braking force is applied to the lancet 183 until the lancet comes to astop at point D. The lancet 183 then recoils in a retrograde directionduring the settling phase of the lancing cycle indicated between D andE. Note that the magnitude of inelastic tenting indicated in FIG. 42 isexaggerated for purposes of illustration.

The amount of inelastic tenting indicated by Z tends to be fairlyconsistent and small compared to the magnitude of the elastic tenting.Generally, the amount of inelastic tenting Z can be about 120 to about140 microns. As the magnitude of the inelastic tenting has a fairlyconstant value and is small compared to the magnitude of the elastictenting for most patients and skin types, the value for the total amountof tenting for the penetration stroke of the lancet 183 is effectivelyequal to the rearward displacement of the lancet during the settlingphase as measured by the processor 193 plus a predetermined value forthe inelastic recoil, such as 130 microns. Inelastic recoil for someembodiments can be about 100 to about 200 microns. The ability tomeasure the magnitude of skin 233 tenting for a patient is important tocontrolling the depth of penetration of the lancet tip 196 as the skinis generally known to vary in elasticity and other parameters due toage, time of day, level of hydration, gender and pathological state.

This value for total tenting for the lancing cycle can then be used todetermine the various characteristics of the patient's skin 233. Once abody of tenting data is obtained for a given patient, this data can beanalyzed in order to predict the total lancet displacement, from thepoint of skin contact, necessary for a successful lancing procedure.This enables the tissue penetration device to achieve a high successrate and minimize pain for the user. A rolling average table can be usedto collect and store the tenting data for a patient with a pointer tothe last entry in the table. When a new entry is input, it can replacethe entry at the pointer and the pointer advances to the next value.When an average is desired, all the values are added and the sum dividedby the total number of entries by the processor 193. Similar techniquesinvolving exponential decay (multiply by 0.95, add 0.05 times currentvalue, etc.) are also possible.

With regard to tenting of skin 233 generally, some typical valuesrelating to penetration depth are now discussed. FIG. 43 shows a crosssectional view of the layers of the skin 233. In order to reliablyobtain a useable sample of blood from the skin 233, it is desirable tohave the lancet tip 196 reach the venuolar plexus of the skin. Thestratum corneum is typically about 0.1 to about 0.6 mm thick and thedistance from the top of the dermis to the venuole plexus can be fromabout 0.3 to about 1.4 mm. Elastic tenting can have a magnitude of up toabout 2 mm or so, specifially, about 0.2 to about 2.0 mm, with anaverage magnitude of about 1 mm. This means that the amount of lancetdisplacement necessary to overcome the tenting can have a magnitudegreater than the thickness of skin necessary to penetrate in order toreach the venuolar plexus. The total lancet displacement from point ofinitial skin contact may have an average value of about 1.7 to about 2.1mm. In some embodiments, penetration depth and maximum penetration depthmay be about 0.5 mm to about 5 mm, specifically, about 1 mm to about 3mm. In some embodiments, a maximum penetration depth of about 0.5 toabout 3 mm is useful.

Referring back to FIG. 29C, in the next operation, represented by theflow diagram box numbered 280 in FIG. 29C, the processor 193 causes awithdraw force to be exerted on the lancet 183 to retract the lancet 183from the skin 233, as shown by arrow 290 in FIG. 36 The processor 193sends a current to an appropriate coil 214-217 so that the coil 214-217exerts an attractive distally oriented force on the magnetic member 202,which should cause the lancet 183 to move backward in the desireddirection. In some embodiments, the lancet 183 is withdrawn with lessforce and a lower speed than the force and speed during the penetrationportion of the operation cycle. Withdrawal speed of the lancet in someembodiments can be about 0.004 to about 0.5 m/s, specifically, about0.006 to about 0.01 m/s. In other embodiments, useful withdrawalvelocities can be about 0.001 to about 0.02 meters per second,specifically, about 0.001 to about 0.01 meters per second. Forembodiments that use a relatively slow withdrawal velocity compared tothe penetration velocity, the withdrawal velocity may up to about 0.02meters per second. For such embodiments, a ratio of the averagepenetration velocity relative to the average withdrawal velocity can beabout 100 to about 1000. In embodiments where a relatively slowwithdrawal velocity is not important, a withdrawal velocity of about 2to about 10 meters per second may be used.

In the next operation, the processor 193 determines whether the lancet183 is moving in the desired backward direction as a result of the forceapplied, as represented by the decision box numbered 281. If theprocessor 193 determines that the lancet 183 is not moving (a “No”result from the decision box 281), then the processor 193 continues tocause a force to be exerted on the lancet 183, as represented by theflow diagram box numbered 282. The processor 193 may cause a strongerforce to be exerted on the lancet 183 or may just continue to apply thesame amount of force. The processor then again determines whether thelancet is moving, as represented by the decision box numbered 283. Ifmovement is still not detected (a “No” result from the decision boxnumbered 283), the processor 193 determines that an error condition ispresent, as represented by the flow diagram box numbered 284. In such asituation, the processor preferably de-energizes the coils to removeforce from the lancet, as the lack of movement may be an indication thatthe lancet is stuck in the skin of the patient and, therefore, that itmay be undesirable to continue to attempt pull the lancet out of theskin.

With reference again to the decision boxes numbered 281 and 283 in FIG.29C, if the processor 193 determines that the lancet is indeed moving inthe desired backward direction away from the skin 233, then the processproceeds to the operation represented by the flow diagram box numbered285. In this operation, the backward movement of the lancet 183continues until the lancet distal end has been completely withdrawn fromthe patient's skin 233. As discussed above, in some embodiments thelancet 183 is withdrawn with less force and a lower speed than the forceand speed during the penetration portion of the operation cycle. Therelatively slow withdrawal of the lancet 183 may allow the blood fromthe capillaries of the patient accessed by the lancet 183 to follow thelancet 183 during withdrawal and reach the skin surface to reliablyproduce a usable blood sample. The process then ends.

Controlling the lancet motion over the operating cycle of the lancet 183as discussed above allows a wide variety of lancet velocity profiles tobe generated by the lancing device 180. In particular, any of the lancetvelocity profiles discussed above with regard to other embodiments canbe achieved with the processor 193, position sensor 191 and driver coilpack 188 of the lancing device 180.

Another example of an embodiment of a velocity profile for a lancet canbe seen in FIGS. 44 and 45, which illustrates a lancet profile with afast entry velocity and a slow withdrawal velocity. FIG. 44 illustratesan embodiment of a lancing profile showing velocity of the lancet versusposition. The lancing profile starts at zero time and position and showsacceleration of the lancet towards the tissue from the electromagneticforce generated from the electromagnetic driver. At point A, the poweris shut off and the lancet 183 begins to coast until it reaches the skin233 indicated by B at which point, the velocity begins to decrease. Atpoint C, the lancet 183 has reached maximum displacement and settlesmomentarily, typically for a time of about 8 milliseconds.

A retrograde withdrawal force is then imposed on the lancet by thecontrollable driver, which is controlled by the processor to maintain awithdrawal velocity of no more than about 0.006 to about 0.01meters/second. The same cycle is illustrated in the velocity versus timeplot of FIG. 45 where the lancet is accelerated from the start point topoint A. The lancet 183 coasts from A to B where the lancet tip 196contacts tissue 233. The lancet tip 196 then penetrates the tissue andslows with braking force eventually applied as the maximum penetrationdepth is approached. The lancet is stopped and settling between C and D.At D, the withdrawal phase begins and the lancet 183 is slowly withdrawnuntil it returns to the initialization point shown by E in FIG. 45. Notethat retrograde recoil from elastic and inelastic tenting was not shownin the lancing profiles of FIGS. 44 and 45 for purpose of illustrationand clarity.

In another embodiment, the withdrawal phase may use a dual speedprofile, with the slow 0.006 to 0.01 meter per second speed used untilthe lancet is withdrawn past the contact point with the tissue, then afaster speed of 0.01 to 1 meters per second may be used to shorten thecomplete cycle.

Referring to FIG. 46, another embodiment of a lancing device including acontrollable driver 294 with a driver coil pack 295, position sensor andlancet 183 are shown. The lancet 297 has a proximal end 298 and a distalend 299 with a sharpened point at the distal end 299 of the lancet 297.A magnetic member 301 disposed about and secured to a proximal endportion 302 of the lancet 297 with a lancet shaft 303 being disposedbetween the magnetic member 301 and the sharpened point 299. The lancetshaft 303 may be comprised of stainless steel, or any other suitablematerial or alloy. The lancet shaft 303 may have a length of about 3 mmto about 50 mm specifically, about 5 mm to about 15 mm.

The magnetic member 301 is configured to slide within an axial lumen 304of the driver coil pack 295. The driver coil pack 295 includes a mostdistal first coil 305, a second coil 306, which is axially disposedbetween the first coil 305 and a third coil 307, and a proximal-mostfourth coil 308. Each of the first coil 305, second coil 306, third coil307 and fourth coil 308 has an axial lumen. The axial lumens of thefirst through fourth coils 305-308 are configured to be coaxial with theaxial lumens of the other coils and together form the axial lumen 309 ofthe driver coil pack 295 as a whole. Axially adjacent each of the coils305-308 is a magnetic disk or washer 310 that augments completion of themagnetic circuit of the coils 305-308 during a lancing cycle of thedriven coil pack 295. The magnetic washers 310 of the embodiment of FIG.46 are made of ferrous steel but could be made of any other suitablemagnetic material, such as iron or ferrite. The magnetic washers 310have an outer diameter commensurate with an outer diameter of the drivercoil pack 295 of about 4.0 to about 8.0 mm. The magnetic washers 310have an axial thickness of about 0.05, to about 0.4 mm, specifically,about 0.15 to about 0.25 mm. The outer shell 294 of the coil pack isalso made of iron or steel to complete the magnetic path around thecoils and between the washers 310.

Wrapping or winding an elongate electrical conductor 311 about the axiallumen 309 until a sufficient number of windings have been achieved formsthe coils 305-308. The elongate electrical conductor 311 is generally aninsulated solid copper wire. The particular materials, dimensions numberof coil windings etc. of the coils 305-308, washers 310 and othercomponents of the driver coil pack 295 can be the same or similar to thematerials, dimensions number of coil windings etc. of the driver coilpack 188 discussed above.

Electrical conductors 312 couple the driver coil pack 295 with aprocessor 313 which can be configured or programmed to control thecurrent flow in the coils 305-308 of the driver coil pack 295 based onposition feedback from the position sensor 296, which is coupled to theprocessor 313 by electrical conductors 315. A power source 316 iselectrically coupled to the processor 313 and provides electrical powerto operate the processor 313 and power the driver coil pack 295. Thepower source 316 may be one or more batteries (not shown) that providedirect current power to the processor 313 as discussed above.

The position sensor 296 is an analog reflecting light sensor that has alight source and light receiver in the form of a photo transducer 317disposed within a housing 318 with the housing 318 secured in fixedspatial relation to the driver coil pack 295. A reflective member 319 isdisposed on or secured to a proximal end 320 of the magnetic member 301.The processor 313 determines the position of the lancet 299 by firstemitting light from the light source of the photo transducer 317 towardsthe reflective member 319 with a predetermined solid angle of emission.Then, the light receiver of the photo transducer 317 measures theintensity of light reflected from the reflective member 319 andelectrical conductors 315 transmit the signal generated therefrom to theprocessor 313.

By calibrating the intensity of reflected light from the reflectivemember 319 for various positions of the lancet 297 during the operatingcycle of the driver coil pack 295, the position of the lancet 297 canthereafter be determined by measuring the intensity of reflected lightat any given moment. In one embodiment, the sensor 296 uses acommercially available LED/photo transducer module such as the OPB703manufactured by Optek Technology, Inc., 1215 W. Crosby Road, Carrollton,Tex., 75006. This method of analog reflective measurement for positionsensing can be used for any of the embodiments of lancet actuatorsdiscussed herein. In addition, any of the lancet actuators or driversthat include coils may use one or more of the coils to determine theposition of the lancet 297 by using a magnetically permeable region onthe lancet shaft 303 or magnetic member 301 itself as the core of aLinear Variable Differential Transformer (LVDT).

Referring to FIGS. 47 and 48, a flat coil lancet driver 325 isillustrated which has a main body housing 326 and a rotating frame 327.The rotating frame 327 pivots about an axle 328 disposed between a base329, a top body portion 330 of the main body housing 326 and disposed ina pivot guide 331 of the rotating frame 327. An actuator arm 332 of therotating frame 327 extends radially from the pivot guide 331 and has alinkage receiving opening 333 disposed at an outward end 334 of theactuator arm 332. A first end 335 of a coupler linkage 336 is coupled tothe linkage receiving opening 333 of the actuator arm 332 and can rotatewithin the linkage receiving opening 333. A second end 337 of thecoupler linkage 336 is disposed within an opening at a proximal end 338of a coupler translation member 341. This configuration allowscircumferential forces imposed upon the actuator arm 332 to betransferred into linear forces on a drive coupler 342 secured to adistal end 343 of the coupler translation member 341. The materials anddimensions of the drive coupler 342 can be the same or similar to thematerials and dimensions of the drive coupler 342 discussed above.

Opposite the actuator arm 332 of the rotating frame 327, a translationsubstrate in the form of a coil arm 344 extends radially from the pivotguide 331 of the rotating frame 327. The coil arm 344 is substantiallytriangular in shape. A flat coil 345 is disposed on and secured to thecoil arm 344. The flat coil 345 has leading segment 346 and a trailingsegment 347, both of which extend substantially orthogonal to thedirection of motion of the segments 346 and 347 when the rotating frame327 is rotating about the pivot guide 331. The leading segment 346 isdisposed within a first magnetically active region 348 generated by afirst upper permanent magnet 349 secured to an upper magnet base 351 anda first lower permanent magnet 352 secured to a lower magnet base 353.The trailing segment 347 is disposed within a second magnetically activeregion 354 generated by a second upper permanent magnet 355 secured tothe upper magnet base 351 and a second lower permanent magnet secured tothe lower magnet base 353.

The magnetic field lines or circuit of the first upper and lowerpermanent magnets 349, 352, 355 and 356 can be directed upward from thefirst lower permanent magnet 352 to the first upper permanent magnet 349or downward in an opposite direction. The magnetic field lines from thesecond permanent magnets 355 and 356 are also directed up or down, andwill have a direction opposite to that of the first upper and lowerpermanent magnets 349 and 352. This configuration produces rotationalforce on the coil arm 344 about the pivot guide 331 with the directionof the force determined by the direction of current flow in the flatcoil 345.

A position sensor 357 includes an optical encoder disk section 358 issecured to the rotating frame 327 which rotates with the rotating frame327 and is read by an optical encoder 359 which is secured to the base329. The position sensor 357 determines the rotational position of therotating frame 327 and sends the position information to a processor 360which can have features which are the same or similar to the features ofthe processor 193 discussed above via electrical leads 361. Electricalconductor leads 363 of the flat coil 345 are also electrically coupledto the processor 360.

As electrical current is passed through the leading segment 346 andtrailing segment 347 of the flat coil 345, the rotational forces imposedon the segments 346 and 347 are transferred to the rotating frame 327 tothe actuator arm 332, through the coupler linkage 336 and couplertranslation member 341 and eventually to the drive coupler 342. In use,a lancet (not shown) is secured into the drive coupler 342, and the flatcoil lancet actuator 325 activated. The electrical current in the flatcoil 345 determines the forces generated on the drive coupler 342, andhence, a lancet secured to the coupler 342. The processor 360 controlsthe electrical current in the flat coil 345 based on the position andvelocity of the lancet as measured by the position sensor 357information sent to the processor 360. The processor 360 is able tocontrol the velocity of a lancet in a manner similar to the processor193 discussed above and can generate any of the desired lancet velocityprofiles discussed above, in addition to others.

FIGS. 49 and 50 depict yet another embodiment of a controlled driver 369having a driver coil pack 370 for a tissue penetration device. Thedriver coil pack 370 has a proximal end 371, a distal end 372 and anaxial lumen 373 extending from the proximal end 371 to the distal end372. An inner coil 374 is disposed about the axial lumen 373 and has atapered configuration with increasing wraps per inch of an elongateconductor 375 in a distal direction. The inner coil 374 extends from theproximal end 371 of the coil driver pack 370 to the distal end 372 ofthe driver coil pack 370 with a major outer diameter or transversedimension of about 1 to about 25 mm, specifically about 1 to about 12mm.

The outer diameter or transverse dimension of the inner coil 374 at theproximal end 371 of the driver coil pack 370 is approximately equal tothe diameter of the axial lumen 373 at the proximal end 371 of the coilpack 370. That is, the inner coil 374 tapers to a reduce outer diameterproximally until there are few or no wraps of elongate electricalconductor 375 at the proximal end 371 of the driver coil pack 370. Thetapered configuration of the inner coil 374 produces an axial magneticfield gradient within the axial lumen 373 of the driver coil pack 370when the inner coil 374 is activated with electrical current flowingthrough the elongate electrical conductor 375 of the inner coil 374.

The axial magnetic field gradient produces a driving force for amagnetic member 376 disposed within the axial lumen 373 that drives themagnetic member 376 towards the distal end 372 of the driver coil pack370 when the inner coil 374 is activated. The driving force on themagnetic member produced by the inner coil 374 is a smooth continuousforce, which can produce a smooth and continuous acceleration of themagnetic member 376 and lancet 377 secured thereto. In some embodiments,the ratio of the increase in outer diameter versus axial displacementalong the inner coil 374 in a distal direction can be from about 1 toabout 0.08, specifically, about 1 to about 0.08.

An outer coil 378 is disposed on and longitudinally coextensive with theinner coil 374. The outer coil 378 can have the same or similardimensions and construction as the inner coil 374, except that the outercoil 378 tapers proximally to an increased diameter or transversedimension. The greater wraps per inch of elongate electrical conductor379 in a proximal direction for the outer coil 378 produces a magneticfield gradient that drives the magnetic member 376 in a proximaldirection when the outer coil 378 is activated with electrical current.This produces a braking or reversing effect on the magnetic member 376during an operational cycle of the lancet 377 and driver coil pack 370.The elongate electrical conductors 375 and 379 of the inner coil 374 andouter coil 378 are coupled to a processor 381, which is coupled to anelectrical power source 382. The processor 381 can have propertiessimilar to the other processors discussed above and can control thevelocity profile of the magnetic member 376 and lancet 377 to produceany of the velocity profiles above as well as others. The driver coilpack 370 can be used as a substitute for the coil driver pack discussedabove, with other components of the lancing device 180 being the same orsimilar.

Embodiments of driver or actuator mechanisms having been described, wenow discuss embodiments of devices which can house lancets, collectsamples of fluids, analyze the samples or any combination of thesefunctions. These front-end devices may be integrated with actuators,such as those discussed above, or any other suitable driver orcontrollable driver.

Generally, most known methods of blood sampling require several steps.First, a measurement session is set up by gathering various articlessuch as lancets, lancet drivers, test strips, analyzing instrument, etc.Second, the patient must assemble the paraphernalia by loading a sterilelancet, loading a test strip, and arming the lancet driver. Third, thepatient must place a finger against the lancet driver and using theother hand to activate the driver. Fourth, the patient must put down thelancet driver and place the bleeding finger against a test strip, (whichmay or may not have been loaded into an analyzing instrument). Thepatient must insure blood has been loaded onto the test strip and theanalyzing instrument has been calibrated prior to such loading. Finally,the patient must dispose of all the blood-contaminated paraphernaliaincluding the lancet. As such, integrating the lancing and samplecollection features of a tissue penetration sampling device can achieveadvantages with regard to patient convenience.

FIG. 51 shows a disposable sampling module 410, which houses the lancet412. The lancet 412 has a head on a proximal end 416 which connects tothe driver 438 and a distal end 414, which lances the skin. The distalend 414 is disposed within the conduit 418. The proximal end 416 extendsinto the cavity 420. The sample reservoir 422 has a narrow input port424 on the ergonomically contoured surface 426, which is adjacent to thedistal end 414 of the lancet 412. The term ergonomically contoured, asused herein, generally means shaped to snugly fit a finger or other bodyportion to be lanced or otherwise tested placed on the surface. Thesampling module 410 is capable of transporting the blood sample from thesample reservoir 422 through small passages (not shown), to ananalytical region 428. The analytical region 428 can include chemical,physical, optical, electrical or other means of analyzing the bloodsample. The lancet, sample flow channel, sample reservoir and analyticalregion are integrated into the sampling module 410 in a single packagedunit.

FIG. 52 shows the chamber 430 in the housing 410′ where the samplingmodule 410 is loaded. The sampling module 410 is loaded on a socket 432suspended with springs 434 and sits in slot 436. A driver 438 isattached to the socket 432. The driver 438 has a proximal end 440 and adistal end 442. The driver 438 can be either a controllable driver ornon-controllable driver any mechanical, such as spring or cam driven, orelectrical, such as electromagnetically or electronically driven, meansfor advancing, stopping, and retracting the lancet. There is a clearance444 between the distal end 442 of the driver 438 and the sensor 446,which is attached to the chamber 430. The socket 432 also contains ananalyzer 448, which is a system for analyzing blood. The analyzer 448corresponds to the analytical region 428 on the module 410 when it isloaded into the socket 432.

FIG. 53 shows a tissue penetration sampling device 411 with the samplingmodule 410 loaded into the socket 432 of housing 410′. The analyticalregion 428 and analyzer 448 overlap. The driver 438 fits into the cavity420. The proximal end 440 of the driver 438 abuts the distal end 416 ofthe lancet 412. The patient's finger 450 sits on the ergonomicallycontoured surface 426.

FIG. 54 shows a drawing of an alternate lancet configuration where thelancet 412 and driver 438 are oriented to lance the side of the finger450 as it sits on the ergonomically contoured surface 426.

FIG. 55 illustrates the orifice 452 and ergonomically contoured surface426. The conduit 418 has an orifice 452, which opens on a blood well454. The sample input port 424 of the reservoir 422 also opens on theblood well 454. The diameter of the sample input port 424 issignificantly greater than the diameter of the orifice 452, which issubstantially the same diameter as the diameter of the lancet 412. Afterthe lancet is retracted, the blood flowing from the finger 450 willcollect in the blood well 454. The lancet 412 will have been retractedinto the orifice 452 effectively blocking the passage of blood down theorifice 452. The blood will flow from the blood well 454 through thesample input port 424 into the reservoir 422.

FIG. 56 shows a drawing of the lancing event. The patient appliespressure by pushing down with the finger 450 on the ergonomicallycontoured surface 426. This applies downward pressure on the samplingmodule 410, which is loaded into the socket 432. As the socket 432 ispushed downward it compresses the springs 434. The sensor 446 makescontact with the distal end 442 of the driver 438 and therebyelectrically detects the presence of the finger on the ergonomicallycontoured surface. The sensor can be a piezoelectric device, whichdetects this pressure and sends a signal to circuit 456, which actuatesthe driver 438 and advances and then retracts the lancet 412 lancing thefinger 450. In another embodiment, the sensor 446 is an electriccontact, which closes a circuit when it contacts the driver 438activating the driver 438 to advance and retract the lancet 412 lancingthe finger 450.

An embodiment of a method of sampling includes a reduced number of stepsthat must be taken by a patient to obtain a sample and analysis of thesample. First, the patient loads a sampling module 410 with an embeddedsterile lancet into the housing device 410′. Second, the patientinitiates a lancing cycle by turning on the power to the device or byplacing the finger to be lanced on the ergonomically contoured surface426 and pressing down. Initiation of the sensor makes the sensoroperational and gives control to activate the launcher.

The sensor is unprompted when the lancet is retracted after its lancingcycle to avoid unintended multiple lancing events. The lancing cycleconsists of arming, advancing, stopping and retracting the lancet, andcollecting the blood sample in the reservoir. The cycle is complete oncethe blood sample has been collected in the reservoir. Third, the patientpresses down on the sampling module, which forces the driver 38 to makecontact with the sensor, and activates the driver 438. The lancet thenpierces the skin and the reservoir collects the blood sample.

The patient is then optionally informed to remove the finger by anaudible signal such as a buzzer or a beeper, and/or a visual signal suchas an LED or a display screen. The patient can then dispose of all thecontaminated parts by removing the sampling module 410 and disposing ofit. In another embodiment, multiple sampling modules 410 may be loadedinto the housing 410′ in the form of a cartridge (not shown). Thepatient can be informed by the tissue penetration sampling device 411 asto when to dispose of the entire cartridge after the analysis iscomplete.

In order to properly analyze a sample in the analytical region 428 ofthe sampling module 410, it may be desirable or necessary to determinewhether a fluid sample is present in a given portion of the sample flowchannel, sample reservoir or analytical area. A variety of devices andmethods for determining the presence of a fluid in a region arediscussed below.

In FIG. 57, a thermal sensor 500 embedded in a substrate 502 adjacent toa surface 504 over which a fluid may flow. The surface may be, forexample, a wall of a channel through which fluid may flow or a surfaceof a planar device over which fluid may flow. The thermal sensor 500 isin electrical communication with a signal-conditioning element 506,which may be embedded in the substrate 502 or may be remotely located.The signal-conditioning element 506 receives the signal from the thermalsensor 500 and modifies it by means such as amplifying it and filteringit to reduce noise. FIG. 57 also depicts a thermal sensor 508 located atan alternate location on the surface where it is directly exposed to thefluid flow.

FIG. 58 shows a configuration of a thermal sensor 500 adjacent to aseparate heating element 510. The thermal sensor 500 and the heatingelement 510 are embedded in a substrate 502 adjacent to a surface 504over which a fluid may flow. In an alternate embodiment, one or moreadditional thermal sensors may be adjacent the heating element and mayprovide for increased signal sensitivity. The thermal sensor 500 is inelectrical communication with a signal-conditioning element 506, whichmay be embedded in the substrate 502 or may be remotely located.

The signal-conditioning element 506 receives the signal from the thermalsensor 500 and modifies it by means such as amplifying it and filteringit to reduce noise. The heating element 510 is in electricalcommunication with a power supply and control element 512, which may beembedded in the substrate 502 or may be remotely located. The powersupply and control element 512 provides a controlled source of voltageand current to the heating element 510.

FIG. 59 depicts a configuration of thermal sensors 500 having threethermal sensor/heating element pairs (500/510), or detector elements,(with associated signal conditioning elements 506 and power supply andcontrol elements 512 as described in FIG. 58) embedded in a substrate502 near each other alongside a surface 504. The figure depicts thethermal sensors 500 arranged in a linear fashion parallel to the surface504, but any operable configuration may be used. In alternateembodiments, fewer than three or more than three thermal sensor/heatingelement pairs (500/510) may be used to indicate the arrival of fluidflowing across a surface 504. In other embodiments, self-heating thermalsensors are used, eliminating the separate heating elements.

Embodiments of the present invention provide a simple and accuratemethodology for detecting the arrival of a fluid at a defined location.Such detection can be particularly useful to define the zero- orstart-time of a timing cycle for measuring rate-based reactions. Thiscan be used in biochemical assays to detect a variety of analytespresent in a variety of types of biological specimens or fluids and forrate-based reactions such as enzymatic reactions. Examples of relevantfluids include, blood, serum, plasma, urine, cerebral spinal fluid,saliva, enzymatic substances and other related substances and fluidsthat are well known in the analytical and biomedical art. The reactionchemistry for particular assays to analyze biomolecular fluids isgenerally well known, and selection of the particular assay used willdepend on the biological fluid of interest.

Assays that are relevant to embodiments of the present invention includethose that result in the measurement of individual analytes or enzymes,e.g., glucose, lactate, creatinine kinase, etc, as well as those thatmeasure a characteristic of the total sample, for example, clotting time(coagulation) or complement-dependent lysis. Other embodiments for thisinvention provide for sensing of sample addition to a test article orarrival of the sample at a particular location within that article.

Referring now to FIG. 60, a substrate 502 defines a channel 520 havingan interior surface 522 over which fluid may flow. An analysis site 524is located within the channel 520 where fluid flowing in the channel 520may contact the analysis site 524. In various embodiments, the analysissite 524 may alternatively be upon the interior surface 522, recessedinto the substrate 502, or essentially flush with the interior surface522. FIG. 60, depicts several possible locations for thermal sensorsrelative the substrate, the channel, and the analysis site; also, otherlocations may be useful and will depend upon the design of the device,as will be apparent to those of skill in art.

In use, thermal sensors may be omitted from one or more of the locationsdepicted in FIG. 60, depending on the intended design. A recess in theanalysis site 524 may provide the location for a thermal sensor 526, asmay the perimeter of the analysis site provide the location for athermal sensor 528. One or more thermal sensors 530, 532, 534 may belocated on the upstream side of the analysis site 524 (as fluid flowsfrom right to left in FIG. 60), or one or more thermal sensors 536, 538,540 may be located on the downstream side of the analysis site 524.

The thermal sensor may be embedded in the substrate near the surface, asthermal sensor 542 is depicted. In various other embodiments, thethermal sensor(s) may be located upon the interior surface, recessedinto the interior surface, or essentially flush with the interiorsurface. Each thermal sensor may also be associated with a signalconditioning element, heating element, and power supply and controlelements, as described above, and a single signal conditioning element,heating element, or power supply and control element may be associatedwith more than one thermal sensor.

FIG. 61 shows possible positions for thermal sensors relative toanalysis sites 524 arranged in an array on a surface 556. A recess inthe analysis site 524 may provide the location for a thermal sensor 544,as may the perimeter of the analysis site provide the location for athermal sensor 546. The edge of the surface surrounding the array ofanalysis sites may provide the position for one or more thermal sensors548. Thermal sensors may be positioned between analysis sites in aparticular row 550 or column 552 of the array, or may be arranged on thediagonal 554.

In various embodiments, the thermal sensor(s) may be may be embedded inthe substrate near the surface or may be located upon the surface,recessed into the surface, or essentially flush with the surface. Eachthermal sensor may also be associated with a signal conditioningelements, heating elements, and power supply and control elements, asdescribed above, and a single signal conditioning element, heatingelement, or power supply and control element may be associated with morethan one thermal sensor.

The use of small thermal sensors can be useful in miniaturized systems,such as microfluidic devices, which perform biomolecular analyses onvery small fluid samples. Such analyses generally include passing abiomolecular fluid through, over, or adjacent to an analysis site andresult in information about the biomolecular fluid being obtainedthrough the use of reagents and/or test circuits and/or componentsassociated with the analysis site.

FIG. 62 depicts several possible configurations of thermal sensorsrelative to channels and analysis sites. The device schematicallydepicted in FIG. 62 may be, e.g., a microfluidic device for analyzing asmall volume of a sample fluid, e.g. a biomolecular fluid. The devicehas a sample reservoir 560 for holding a quantity of a sample fluid. Thesample fluid is introduced to the sample reservoir 560 via a sampleinlet port 562 in fluid communication with the sample reservoir 560. Athermal sensor 564 is located in or near the sample inlet port 562. Aprimary channel 566 originates at the sample reservoir 560 andterminates at an outflow reservoir 568.

One or more supplemental reservoirs 570 are optionally present and arein fluid communication with the primary channel 566 via one or moresupplemental channels 572, which lead from the supplemental reservoir570 to the primary channel 566. The supplemental reservoir 570 functionsto hold fluids necessary for the operation of the assay, such as reagentsolutions, wash solutions, developer solutions, fixative solutions, etcetera. In the primary channel 566 at a predetermined distance from thesample reservoir 560, an array of analysis sites 574 is present.

Thermal sensors are located directly upstream (as fluid flows from rightto left in the figure) from the array 576 and directly downstream fromthe array 578. Thermal sensors are also located in the primary channeladjacent to where the primary channel originates at the sample reservoir580 and adjacent to where the primary channel terminates at the outflowreservoir 582. The supplemental channel provides the location foranother thermal sensor 584.

When the device is in operation, the thermal sensor 564 located in ornear the sample inlet port 562 is used to indicate the arrival of thesample fluid, e.g. the biomolecular fluid, in the local environment ofthe thermal sensor, as described herein, and thus provides confirmationthat the sample fluid has successfully been introduced into the device.The thermal sensor 580 located in the primary channel 566 adjacent towhere the primary channel 566 originates at the sample reservoir 560produces a signal indicating that sample fluid has started to flow fromthe sample reservoir 560 into the primary channel 566. The thermalsensors 576 in the primary channel 566 just upstream from the array ofanalysis sites 574 may be used to indicate that the fluid sample isapproaching the array 574. Similarly, the thermal sensors 578 in theprimary channel 566 just downstream from the array of analysis sites 574may be used to indicate that the fluid sample has advanced beyond thearray 574 and has thus contacted each analysis site.

The thermal sensor 584 in the supplemental channel 572 providesconfirmation that the fluid contained within the supplemental reservoir570 has commenced to flow therefrom. The thermal sensor 582 in theprimary channel 566 adjacent to where the primary channel 566 terminatesat the outflow reservoir 568 indicates when sample fluid arrives nearthe outflow reservoir 568, which may then indicate that sufficientsample fluid has passed over the array of analysis sites 574 and thatthe analysis at the analysis sites is completed.

Embodiments of the invention provide for the use of a thermal sensor todetect the arrival of the fluid sample at a determined region, such asan analysis site, in the local environment of the thermal sensor nearthe thermal sensor. A variety of thermal sensors may be used.Thermistors are thermally-sensitive resistors whose prime function is todetect a predictable and precise change in electrical resistance whensubjected to a corresponding change in temperature Negative TemperatureCoefficient (NTC) thermistors exhibit a decrease in electricalresistance when subjected to an increase in temperature and PositiveTemperature Coefficient (PTC) thermistors exhibit an increase inelectrical resistance when subjected to an increase in temperature.

A variety of thermistors have been manufactured for over the counter useand application. Thermistors are capable of operating over thetemperature range of −100 degrees to over 600 degrees Fahrenheit.Because of their flexibility, thermistors are useful for application tomicro-fluidics and temperature measurement and control.

A change in temperature results in a corresponding change in theelectrical resistance of the thermistor. This temperature change resultsfrom either an external transfer of heat via conduction or radiationfrom the sample or surrounding environment to the thermistor, or as aninternal application of heat due to electrical power dissipation withinthe device. When a thermistor is operated in “self-heating” mode, thepower dissipated in the device is sufficient to raise its temperatureabove the temperature of the local environment, which in turn moreeasily detects thermal changes in the conductivity of the localenvironment.

Thermistors are frequently used in “self heating” mode in applicationssuch as fluid level detection, airflow detection and thermalconductivity materials characterization. This mode is particularlyuseful in fluid sensing, since a self-heating conductivity sensordissipates significantly more heat in a fluid or in a moving air streamthan it does in still air.

Embodiments of the invention may be designed such that the thermalsensor is exposed directly to the sample. However, it may also beembedded in the material of the device, e.g., in the wall of a channelmeant to transport the sample. The thermal sensor may be covered with athin coating of polymer or other protective material.

Embodiments of the device need to establish a baseline or thresholdvalue of a monitored parameter such as temperature. Ideally this isestablished during the setup process. Once fluid movement has beeninitiated, the device continuously monitors for a significant changethereafter. The change level designated as “significant” is designed asa compromise between noise rejection and adequate sensitivity. Theactual definition of the “zero- or start-time” may also include analgorithm determined from the time history of the data, i.e., it can bedefined ranging from the exact instant that a simple threshold iscrossed, to a complex mathematical function based upon a time sequenceof data.

In use, a signal is read from a thermal sensor in the absence of thesample or fluid. The fluid sample is then introduced. The sample flowsto or past the site of interest in the local environment of the thermalsensor, and the thermal sensor registers the arrival of the sample. Thesite of interest may include an analysis site for conducting, e.g., anenzymatic assay. Measuring the arrival of fluid at the site of interestthus indicates the zero- or start-time of the reaction to be performed.For detection of fluid presence, these sites may be any of a variety ofdesired locations along the fluidic pathway. Embodiments of theinvention are particularly well suited to a microfluidic cartridge orplatform, which provide the user with an assurance that a fluid samplehas been introduced and has flowed to the appropriate locations in theplatform.

A rate-based assay must measure both an initiation time, and some numberof later time points, one of which is the end-point of the assay.Therefore, baseline or threshold value can be established, and thencontinuously monitored for a significant change thereafter; one suchchange is the arrival of the fluid sample that initiates the enzymereaction. Baseline values are frequently established during the devicesetup process. The threshold is designed as a compromise between noiserejection and adequate sensitivity. The defined zero- or “start-time”can be defined ranging from the exact instant that a simple threshold iscrossed, to the value algorithmically determined using a filter based ona time sequence of data.

Embodiments of the invention accomplish this in a variety of ways. Inone embodiment, an initial temperature measurement is made at a thermalsensor without the sample present. The arrival of a sample changescauses the thermal sensor to register a new value. These values are thencompared.

Another embodiment measures the change in thermal properties (such asthermal conductivity or thermal capacity) in the local environment of athermal sensor caused by the arrival of a fluid sample. In general thisis the operating principle of a class of devices known as “thermalconductivity sensors” or “heat flux sensors”. At least two hardwareimplementations have been used and are described above. Oneimplementation utilizes a thermal sensor in a “self-heating mode.” In“self-heating mode,” a self-heating thermal sensor may utilize apositive temperature coefficient thermistor placed in or near the flowchannel, e.g. located in the wall of the flow channel.

An electrical current is run through the thermistor, causing the averagetemperature of the thermistor to rise above that of the surroundingenvironment. The temperature can be determined from the electricalresistance, since it is temperature dependent. When fluid flows throughthe channel, it changes the local thermal conductivity near thethermistor (usually to become higher) and this causes a change in theaverage temperature of the thermistor. It also changes the thermalcapacity, which modifies the thermal dynamic response. These changesgive rise to a signal, which can be detected electronically bywell-known means, and the arrival of the fluid can thereby be inferred.

A second hardware implementation requires a separate heating element inor near the flow channel, plus a thermal sensor arrangement in closeproximity. Passing a current through the element provides heat to thelocal environment and establishes a local temperature detected by thethermocouple device. This temperature or its dynamic response is alteredby the arrival of the fluid or blood in or near the local environment,similar to the previously described implementation, and the event isdetected electronically.

The heating element can be operated in a controlled input mode, whichmay include controlling one or more of the following parameters—appliedcurrent, voltage or power—in a prescribed manner. When operating incontrolled input mode, fluctuations of the temperature of the thermalsensor are monitored in order to detect the arrival of the fluid.

Alternatively, the heating element can be operated in such a fashion asto control the temperature of the thermal sensor in a prescribed manner.In this mode of operation, the resulting fluctuations in one or more ofthe input parameters to the heating element (applied current, voltage,and power) can be monitored in order to detect the arrival of the fluid.

In either of the above-described operating modes, the prescribedparameter can be held to a constant value or sequence of values that areheld constant during specific phases of operation of the device. Theprescribed parameter can also varied as a known function or waveform intime.

The change in the monitored parameters caused by the arrival of thefluid can be calculated in any of a number of ways, using methods wellknown in the art of signal processing. The signal processing methodsallow the relation of the signal received prior to arrival of the fluidwith the signal received upon arrival of the fluid to indicate that thefluid has arrived. For example, and after suitable signal filtering isapplied, changes in the monitored value or the rate of change of thevalue of the signal can be monitored to detect the arrival of the fluid.Additionally, the arrival of fluid will cause a dynamic change in thethermodynamic properties of the local environment, such as thermalconductivity or thermal capacity. When the input parameter is a timevarying function this change of thermodynamic properties will cause aphase shift of the measured parameter relative to the controlledparameter. This phase shift can be monitored to detect the arrival ofthe fluid.

It should also be noted that sensitivity to thermal noise and operatingpower levels could be reduced in these either of these modes ofoperation by a suitable choice of time-varying waveforms for theprescribed parameter, together with appropriate and well-known signalprocessing methods applied to the monitored parameters. However, thesepotential benefits may come at the cost of slower response time.

Referring to FIG. 63, an alternative embodiment of a tissue penetrationsampling device is shown which incorporates disposable sampling module590, a lancet driver 591, and an optional module cartridge 592 areshown. The optional module cartridge comprises a case body 593 having astorage cavity 594 for storing sampling. modules 590. A cover to thiscavity has been left out for clarity. The cartridge further comprises achamber 595 for holding the lancet driver 591. The lancet driver has apreload adjustment knob 596, by which the trigger point of the lancetdriver may be adjusted. This insures a reproducible tension on thesurface of the skin for better control of the depth of penetration andblood yield. In one embodiment, the sampling module 590 is removablyattached to the lancet driver 591, as shown, so that the sampling module590 is disposable and the lancet driver 591 is reusable. In analternative embodiment, the sampling module and lancet driver arecontained within a single combined housing, and the combination sampleacquisition module/lancet driver is disposable. The sampling module 590includes a sampling site 597, preferably having a concave depression598, or cradle, that can be ergonomically designed to conform to theshape of a user's finger or other anatomical feature (not shown).

The sampling site further includes an opening 599 located in the concavedepression. The lancet driver 591 is used to fire a lancet containedwithin and guided by the sampling module 590 to create an incision onthe user's finger when the finger is placed on the sampling site 597. Inone embodiment, the sampling site forms a substantially airtight seal atthe opening when the skin is firmly pressed against the sampling site;the sampling site may additionally have a soft, compressible materialsurrounding the opening to further limit contamination of the bloodsample by ambient air. “Substantially airtight” in this context meansthat only a negligible amount of ambient air may leak past the sealunder ordinary operating conditions, the substantially airtight sealallowing the blood to be collected seamlessly.

Referring to FIGS. 64 and 65, the lancet 600 is protected in theintegrated housing 601 that provides a cradle 602 for positioning theuser's finger or other body part, a sampling port 603 within the cradle602, and a sample reservoir 603′ for collecting the resulting bloodsample. The lancet 600 is a shaft with a distal end 604 sharpened toproduce the incision with minimal pain. The lancet 600 further has anenlarged proximal end 605 opposite the distal end. Similar lancets arecommonly known in the art.

Rather than being limited to a shaft having a sharp end, the lancet mayhave a variety of configurations known in the art, with suitablemodifications being made to the system to accommodate such other lancetconfigurations, such configurations having a sharp instrument that exitsthe sampling port to create a wound from which a blood sample may beobtained.

In the figures, the lancet 600 is slidably disposed within a lancetguide 606 in the housing 601, and movement of the lancet 600 within thelancet guide 606 is closely controlled to reduce lateral motion of thelancet, thereby reducing the pain of the lance stick. The sampleacquisition module also includes a return stop 613, which retains thelancet within the sample acquisition module. The sampling module has anattachment site 615 for attachment to the lancet driver.

The sampling module further includes a depth selector allowing the userto select one of several penetration depth settings. The depth selectoris shown as a multi-position thumbwheel 607 having a graduated surface.By rotating the thumbwheel 607, the user selects which part of thegraduated surface contacts the enlarged proximal end 605 of the lancetto limit the movement of the lancet 600 within the lancet guide 606.

The thumbwheel is maintained in the selected position by a retainer 608having a protruding, rounded surface which engages at least one ofseveral depressions 609 (e.g. dimples, grooves, or slots) in thethumbwheel 607. The depressions 609 are spatially aligned to correspondwith the graduated slope of the thumbwheel 607, so that, when thethumbwheel 607 is turned, the depth setting is selected and maintainedby the retainer 608 engaging the depression 609 corresponding to theparticular depth setting selected.

In alternate embodiments, the retainer may be located on the depthselector and the depressions corresponding to the depth setting locatedon the housing such that retainer may functionally engage thedepressions. Other similar arrangements for maintaining components inalignment are known in the art and may be used. In further alternateembodiments, the depth selector may take the form of a wedge having agraduated slope, which contacts the enlarged proximal end of the lancet,with the wedge being retained by a groove in the housing.

The sample reservoir 603′ includes an elongate, rounded chamber 610within the housing 601 of the sample acquisition module. The chamber 610has a flat or slightly spherical shape, with at least one side of thechamber 610 being formed by a smooth polymer, preferably absent of sharpcorners. The sample reservoir 603′ also includes a sample input port 611to the chamber 610, which is in fluid communication with the samplingport 603, and a vent 612 exiting the chamber.

A cover (not shown), preferably of clear material such as plastic,positions the lancet 600 and closes the chamber 603′, forming anopposing side of the chamber 603′. In embodiments where the cover isclear, the cover may serve as a testing means whereby the sample may beanalyzed in the reservoir via optical sensing techniques operatingthrough the cover. A clear cover will also aid in determining byinspection when the sample reservoir is full of the blood sample.

FIG. 66 shows a portion of the sampling module illustrating an alternateembodiment of the sample reservoir. The sample reservoir has a chamber616 having a sample input port 617 joining the chamber 616 to a bloodtransport capillary channel 618; the chamber 616 also has a vent 619.The chamber has a first side 620 that has a flat or slightly sphericalshape absent of sharp corners and is formed by a smooth polymer. Anelastomeric diaphragm 621 is attached to the perimeter of the chamber616 and preferably is capable of closely fitting to the first side ofthe chamber 620.

To control direction of blood flow, the sample reservoir is providedwith a first check valve 622 located at the entrance 617 of the samplereservoir and a second check valve 623 leading to an exit channel 624located at the vent 619. Alternately, a single check valve (at thelocation 622) may be present controlling both flow into the chamber 616via the blood transport capillary channel 618 and flow out of thechamber. 616 into an optional alternate exit channel 625. The samplereservoir has a duct 626 connecting to a source of variable pressurefacilitating movement of the diaphragm 621.

When the diaphragm 621 is flexed away from the first side of the chamber620 (low pressure supplied from the source via duct 626), the firstcheck valve 622 is open and the second check valve 623 is closed,aspiration of the blood sample into the sample reservoir follows. Whenthe diaphragm 621 is flexed in the direction of the first side of thechamber 620 (high pressure supplied from the source via duct 626) withthe first check valve 622 closed and the second check valve 623 open,the blood is forced out of the chamber 616. The direction of movementand actuation speed of the diaphragm 621 can be controlled by thepressure source, and therefore the flow of the sample can be acceleratedor decelerated. This feature allows not only reduced damage to the bloodcells but also for the control of the speed by which the chamber 616 isfilled.

While control of the diaphragm 621 via pneumatic means is described inthis embodiment, mechanical means may alternately be used. Essentially,this micro diaphragm pump fulfills the aspiration, storage, and deliveryfunctions. The diaphragm 621 may be used essentially as a pump tofacilitate transfer of the blood to reach all areas required. Suchrequired areas might be simple sample storage areas further downstreamfor assaying or for exposing the blood to a chemical sensor or othertesting means. Delivery of the blood may be to sites within the samplingmodule or to sites outside the sampling module, i.e. a separate analysisdevice.

In an alternate embodiment, a chemical sensor or other testing means islocated within the sampling module, and the blood is delivered to thechemical sensor or other testing means via a blood transfer channel influid communication with the sample reservoir. The components of thesampling module may be injection molded and the diaphragm may be fusedor insertion molded as an integral component.

FIG. 67 depicts a portion of the disposable sampling module surroundingthe sampling port 627, including a portion of the sampling site cradlesurface 628. The housing of the sampling module includes a primarysample flow channel 629 that is a capillary channel connecting thesample input port to the sample reservoir. The primary sample flowchannel 629 includes a primary channel lumenal surface 630 and a primarychannel entrance 631, the primary channel entrance 631 opening into thesample input port 627. The sampling module may optionally include asupplemental sample flow channel 632 that is also a capillary channelhaving a supplemental channel lumenal surface 633 and a supplementalchannel entrance 634, the supplemental channel entrance 634 opening intothe sample input port 627.

The primary sample flow channel 629 has a greater cross-sectional areathan the supplemental sample flow channel 632, preferably by at least afactor of two. Thus, the supplemental sample flow channel 632 drawsfluid faster than the primary sample flow channel 629. When the firstdroplet of blood is received into the sample input port 627, themajority of this droplet is drawn through the supplemental sample flowchannel 632. However, as the blood continues to flow from the incisioninto the sample input port 627, most of this blood is drawn through theprimary sample flow channel 629, since the supplemental sample flowchannel 632 is of limited capacity and is filled or mostly filled withthe first blood droplet. This dual capillary channel configuration isparticularly useful in testing where there is a concern withcontamination of the sample, e.g. with debris from the lancet strike or(particularly in the case of blood gas testing) with air.

In order to improve blood droplet flow, some priming or wicking of thesurface with blood is at times necessary to begin the capillary flowprocess. Portions of the surfaces of the sample input port 627 and theprimary and supplemental (if present) sample flow channels 629, 632 aretreated to render those surfaces hydrophilic. The surface modificationmay be achieved using mechanical, chemical, corona, or plasma treatment.Examples of such coatings and methods are marketed by AST Products(Billerica, Mass.) and Spire Corporation (Bedford, Mass.).

However, a complete blanket treatment of the surface could provedetrimental by causing blood to indiscriminately flow all over thesurface and not preferentially through the capillary channel(s). Thisultimately will result in losses of blood fluid. The particular surfaceswhich receive the treatment are selected to improve flow of blood froman incised finger on the sampling site cradle surface 628 through thesample input port 627 and at least one of the sample flow channels 629,632 to the sample reservoir. Thus, the treatment process should bemasked off and limited only to the selected surfaces. The maskingprocess of selectively modifying the sampling surface from hydrophobicto hydrophilic may be done with mechanical masking techniques such aswith metal shielding, deposited dielectric or conductive films, orelectrical shielding means.

In some embodiments, the treated surfaces are limited to one or more ofthe following: the surface of the sampling port which lies between thesampling site cradle surface and the primary and supplemental sampleflow channel, the surface immediately adjacent to the entrances to theprimary and/or supplemental sample flow channels 631, 634 (both withinthe sample input port and within the sample flow channel), and thelumenal surface of the primary and/or supplemental sample flow channels630, 633.

Upon exiting the incision blood preferentially moves through the sampleinput port 627 into the supplementary sample flow channel 632 (ifpresent) and into the primary sample flow channel 629 to the samplereservoir, resulting in efficient capture of the blood. Alternatively,the substrate material may be selected to be hydrophilic or hydrophobic,and a portion of the surface of the substrate material may be treatedfor the opposite characteristic.

In an embodiment, FIG. 67 a membrane 635 at the base of the sample inputport 627 is positioned between the retracted sharpened distal end of thelancet 636 and the entrance to the sample flow channels 631, 634. Themembrane 635 facilitates the blood sample flow through the sample flowchannels 629, 632 by restricting the blood from flowing into the area636 surrounding the distal end of the lancet 637. The blood thus flowspreferentially into the sample reservoir. In an embodiment, the membrane635 is treated to have a hydrophobic characteristic. In anotherembodiment, the membrane 635 is made of polymer-based film 638 that hasbeen coated with a silicone-based gel 639.

For example, the membrane structure may comprise a polymer-based film638 composed of polyethylene terephthalate, such as the film sold underthe trademark MYLAR. The membrane structure may further comprise a thincoating of a silicone-based gel 639 such as the gel sold under thetrademark SYLGARD on at least one surface of the film. The usefulness ofsuch a film is its ability to reseal after the lancet has penetrated itwithout physically affecting the lancet's cutting tip and edges. TheMYLAR film provides structural stability while the thin SYLGARD siliconelaminate is flexible enough to retain its form and close over the holemade in the MYLAR film. Other similar materials fulfilling thestructural stability and flexibility roles may be used in themanufacture of the membrane in this embodiment.

The membrane 635 operates to allow the sharpened distal end of thelancet 637 to pierce the membrane as the sharpened distal end of thelancet 637 travels into and through the sample input port 627. In anembodiment, the silicone-based gel 639 of the membrane 635 automaticallyseals the cut caused by the piercing lancet. Therefore, after anincision is made on a finger of a user, the blood from the incision isprevented from flowing through the membrane 635, which aids the blood totravel through the primary sample flow channel 629 to accumulate withinthe sample reservoir. Thus the film prevents any blood from flowing intothe lancet device assembly, and blood contamination and loss into thelancet device mechanism cavity are prevented. Even without the resealinglayer 639, the hydrophobic membrane 635 deters the flow of blood acrossthe membrane 635, resulting in improved flow through the primary sampleflow channel 629 and reduced or eliminated flow through the piercedmembrane 635.

FIGS. 68-70 illustrate one implementation of a lancet driver 640 atthree different points during the use of the lancet driver. In thisdescription of the lancet driver, proximal indicates a positionrelatively close to the site of attachment of the sampling module;conversely, distal indicates a position relatively far from the site ofattachment of the sampling module. The lancet driver has a driver handlebody 641 defining a cylindrical well 642 within which is a preloadspring 643. Proximal to the preload spring 643 is a driver sleeve 644,which closely fits within and is slidably disposed within the well 642.The driver sleeve 644 defines a cylindrical driver chamber 645 withinwhich is an actuator spring 646. Proximal to the actuator spring 646 isa plunger sleeve 647, which closely fits within and is slidably disposedwithin the driver sleeve 644.

The driver handle body 641 has a distal end 648 defining a threadedpassage 649 into which a preload screw 650 fits. The preload screwdefines a counterbore 651. The preload screw 650 has a distal end 652attached to a preload adjustment knob 653 and a proximal end 654defining an aperture 655. The driver sleeve 644 has a distal end 656attached to a catch fitting 657. The catch fitting 657 defines a catchhole 658. The driver sleeve 644 has a proximal end 659 with a slopedring feature 660 circling the interior surface of the driver sleeve'sproximal end 659.

The lancet driver includes a plunger stem 660 having a proximal end 661and a distal end 662. At its distal end 662, an enlarged plunger head663 terminates the plunger stem 660. At its proximal end 661, theplunger stem 660 is fixed to the plunger tip 667 by adhesively bonding,welding, crimping, or threading into a hole 665 in the plunger tip 667.A plunger hook 665 is located on the plunger stem 660 between theplunger head 663 and the plunger tip 667. The plunger head 663 isslidably disposed within the counterbore 651 defined by the preloadscrew 650. The plunger stem 660 extends from the plunger head 663,through the aperture 655 defined by the proximal end 654 of the preloadscrew, thence through the hole 658 in the catch fitting 657, to thejoint 664 in the plunger tip 667. For assembly purposes, the plungerbase joint 664 may be incorporated into the plunger sleeve 647, and theplunger stem 660 attached to the plunger base 664 by crimping, swaging,gluing, welding, or some other means. Note that the lancet driver 640could be replaced with any of the controlled electromagnetic driversdiscussed above.

The operation of the tissue penetration sampling device may be describedas follows, with reference to FIGS. 63-70. In operation, a freshsampling module 590 is removed from the storage cavity 594 and adjustedfor the desired depth setting using the multi-position thumbwheel 607.The sampling module 590 is then placed onto the end of the lancet driver591. The preload setting may be checked, but will not change from cycleto cycle once the preferred setting is found; if necessary, the preloadsetting may be adjusted using the preload adjustment knob 596.

The combined sampling module and lancet driver assembly is then pressedagainst the user's finger (or other selected anatomical feature) in asmooth motion until the preset trigger point is reached. The triggerpoint corresponds to the amount of preload force that needs to beovercome to actuate the driver to drive the lancet towards the skin. Thepreload screw allows the preload setting to be adjusted by the user suchthat a consistent, preset (by the user) amount of preload force isapplied to the sampling site 597 each time a lancing is performed.

When the motion to press the assembly against the user's finger is begun(see FIG. 68), the plunger hook 665 engages catch fitting 657, holdingthe actuator spring 646 in a cocked position while the force against thefinger builds as the driver sleeve 644 continues to compress the preloadspring 643. Eventually (see FIG. 69) the sloped back of the plunger hook665 slides into the hole 655 in the proximal end of the preload screw654 and disengages from the catch fitting 657. The plunger sleeve 647 isfree to move in a proximal direction once the plunger hook 665 releases,and the plunger sleeve 647 is accelerated by the actuator spring 646until the plunger tip 667 strikes the enlarged proximal end of thelancet 212.

Upon striking the enlarged proximal end of the lancet 605, the plungertip 667 of the actuated lancet driver reversibly engages the enlargedproximal end of the lancet 605. This may be accomplished by mechanicalmeans, e.g. a fitting attached to the plunger tip 667 that detachablyengages a complementary fitting on the enlarged proximal end of thelancet 605, or the enlarged proximal end of the lancet 605 may be coatedwith an adhesive that adheres to the plunger tip 667 of the actuatedlancet driver. Upon being engaged by the plunger tip 667, the lancet 600slides within the lancet guide 606 with the sharpened distal end of thelancet 604 emerging from the housing 601 through the sampling port 603to create the incision in the user's finger.

At approximately the point where the plunger tip 667 contacts theenlarged proximal end of the lancet 605, the actuator spring 646 is atits relaxed position, and the plunger tip 667 is traveling at itsmaximum velocity. During the extension stroke, the actuator spring 646is being extended and is slowing the plunger tip 667 and lancet 600. Theend of stroke occurs (see FIG. 70) when the enlarged proximal end of thelancet 605 strikes the multi-position thumbwheel 607.

The direction of movement of the lancet 600 is then reversed and theextended actuator spring then quickly retracts the sharpened distal endof the lancet 604 back through the sampling port 603. At the end of thereturn stroke, the lancet 600 is stripped from the plunger tip 667 bythe return stop 613. The adhesive adheres to the return stop 613retaining the lancet in a safe position.

As blood seeps from the wound, it fills the sample input port 603 and isdrawn by capillary action into the sample reservoir 603′. In thisembodiment, there is no reduced pressure or vacuum at the wound, i.e.the wound is at ambient air pressure, although embodiments which drawthe blood sample by suction, e.g. supplied by a syringe or pump, may beused. The vent 612 allows the capillary action to proceed until theentire chamber is filled, and provides a transfer port for analysis ofthe blood by other instrumentation. The finger is held against thesample acquisition module until a complete sample is observed in thesample reservoir.

As the sampling module 600 is removed from the lancet driver 591, alatch 614 that is part of the return stop 613 structure engages a slopedring feature 660 inside the lancet driver 591. As the lancet driver 591is removed from the sampling module 600, the latch forces the returnstop 613 to rotate toward the lancet 600, bending it to lock it in asafe position, and preventing reuse.

As the sampling module 600 is removed from the lancet driver 591, thedriver sleeve 644 is forced to slide in the driver handle body 641 byenergy stored in the preload spring 643. The driver sleeve 644, plungersleeve 647, and actuator spring 646 move outward together until theplunger head 663 on the plunger stem 660 contacts the bottom of thecounterbore 651 at the proximal end of the preload screw 654. Thepreload spring 643 continues to move the driver sleeve 644 outwardcompressing the actuator spring 646 until the plunger hook 665 passesthrough the hole 658 in the catch fitting 657. Eventually the twosprings reach equilibrium and the plunger sleeve 647 comes to rest in acocked position.

After the sampling module 600 is removed from the lancet driver 591, itmay be placed in a separate analysis device to obtain blood chemistryreadings. In a preferred embodiment, the integrated housing 601 orsample reservoir 603′ of the sampling module 600 contains at least onebiosensor, which is powered by and/or read by the separate analysisdevice. In another embodiment, the analysis device performs an opticalanalysis of the blood sample directly through the clear plastic cover ofthe sampling module. Alternatively, the blood sample may be transferredfrom the sampling module into an analysis device for distribution tovarious analysis processes.

Alternate embodiments of the invention offer improved success rates forsampling, which reduces the needless sacrifice of a sample storagereservoir or an analysis module due to inadequate volume fill. Alternateembodiments allow automatic verification that sufficient blood has beencollected before signaling the user (e.g. by a signal light or anaudible beep) that it is okay to remove the skin from the sampling site.In such alternate embodiments, one or more additional lancet(s) (denotedbackup lancets) and/or lancet driver(s) (denoted backup lancet drivers)and/or sample reservoir(s) (denoted backup sample reservoirs) arepresent with the “primary” sampling module.

In one such preferred embodiment, following detection of inadequateblood sample volume (e.g., by light or electronic methods), a backupsampling cycle is initiated automatically. The “backup sampling cycle”includes disconnecting the primary sample reservoir via a simple valvingsystem, bringing the backup components online, lancing of the skin,collection of the blood, and movement of the blood to the backup samplereservoir.

Blood flows into the backup sample reservoir until the required volumeis obtained. The cycle repeats itself, if necessary, until the correctvolume is obtained. Only then is the sample reservoir made available asa source of sampled blood for use in measurements or for otherapplications. The series of reservoirs and/or lancets and/or lancetdrivers may easily be manufactured in the same housing and betransparent to the user.

In one embodiment, up to three sample reservoirs (the primary plus twobackup) are present in a single sample acquisition module, eachconnected via a capillary channel/valving system to one or more samplingports. Another embodiment has four sample reservoirs (the primary plusthree backup) present in a single sample acquisition module, eachconnected via a capillary channel/valving system to one or more samplingports. With three or four sample reservoirs, at least an 80% samplingsuccess rate can be achieved for some embodiments.

Another embodiment includes a miniaturized version of the tissuepenetration sampling device. Several of the miniature lancets may belocated in a single sampling site, with corresponding sample flowchannels to transfer blood to one or more reservoirs. The sample flowchannels may optionally have valves for controlling flow of blood. Thedevice may also include one or more sensors, such as the thermal sensorsdiscussed above, for detecting the presence of blood, e.g. to determineif a sufficient quantity of blood has been obtained. In such anembodiment, the disposable sampling module, the lancet driver, and theoptional module cartridge will have dimensions no larger than about 150mm long, 60 mm wide, and 25 mm thick.

In other embodiments, the size of the tissue penetration sampling deviceincluding the disposable sampling module, the lancet driver, and theoptional cartridge will have dimensions no larger than about 100 mmlong, about 50 mm wide, and about 20 mm thick, and in still otherembodiments no larger than about 70 mm. long, about 30 mm wide, andabout 10 mm thick. The size of the tissue penetration sampling deviceincluding the disposable sampling module, the lancet driver, and theoptional cartridge will generally be at least about 10 mm long, about 5mm wide, and about 2 mm thick.

In another miniature embodiment, the dimensions of the lancet driverwithout the cartridge or sampling module are no larger than about 80 mmlong, 10 mm wide, and 10 mm thick, or specifically no larger than about50 mm long, 7 mm wide, and 7 mm thick, or even more specifically nolarger than about 15 mm long, 5 mm wide, and 3 mm thick; dimensions ofthe lancet driver without the cartridge or sampling module are generallyat least about 1 mm long, 0.1 mm wide, and 0.1 mm thick, or specificallyat least about 2 mm long, 0.2 mm wide, and 0.2 mm thick, or morespecifically at least about 4 mm long, 0.4 mm wide, and 0.4 mm thick.

In yet another miniature embodiment, dimensions of the miniaturesampling module without the lancet driver or cartridge are no largerthan about 15 mm long, about 10 mm wide, and about 10 mm thick, or nolarger than about 10 mm long, about 7 mm wide, and about 7 mm thick, orno larger than about 5 mm long, about 3 mm wide, and about 2 mm thick;dimensions of the miniature sampling module without the lancet driver orcartridge are generally at least about 1 mm long, 0.1 mm wide, and 0.1mm thick, specifically at least about 2 mm long, 0.2 mm wide, and 0.2 mmthick, or more specifically at least about 4 mm long, 0.4 mm wide, and0.4 mm thick.

In another embodiment, the miniaturized sampling module and the lancetdriver form a single unit having a shared housing, and the combinedsample acquisition module/lancet driver unit is disposable. Such acombined unit is no larger than about 80 mm long, about 30 mm wide, andabout 10 mm thick, specifically no larger than about 50 mm long, about20 mm wide, and about 5 mm thick, more specifically, no larger thanabout 20 mm long, about 5 mm wide, and about 3 mm thick; the combinedunit is generally at least about 2 mm long, about 0.3 mm wide, and about0.2 mm thick, specifically at least about 4 mm long, 0.6 mm wide, and0.4 mm thick, more specifically, at least about 8 mm long, 1 mm wide,and 0.8 mm thick.

Referring to FIG. 71, another embodiment of a tissue penetrationsampling device is shown, incorporating a disposable sampling module 608cartridge and analyzer-device 669 is shown. The analyzer device 669includes a deck 670 having a lid 671 attached to the deck by hingesalong the rear edge of the system 672. A readout display 673 on the lid671 functions to give the user information about the status of theanalyzer device 669 and/or the sampling module cartridge 668, or to givereadout of a blood test. The analyzer device 669 has several functionbuttons 674 for controlling function of the analyzer device 669 or forinputting information into the reader device 669. Alternatively, thereader device may have a touch-sensitive screen, an optical scanner, orother input means known in the art.

An analyzer device with an optical scanner may be particularly useful ina clinical setting, where patient information may be recorded using scancodes on patients' wristbands or files. The analyzer reader device mayhave a memory, enabling the analyzer device to store results of manyrecent tests. The analyzer device may also have a clock and calendarfunction, enabling the results of tests stored in the memory to be timeand date-stamped. A computer interface 675 enables records in memory tobe exported to a computer. The analyzer device 669 has a chamber locatedbetween the deck 670 and the lid 671, which closely accommodates asampling module cartridge 668. Raising the lid 671, allowing a samplingmodule cartridge 668 to be inserted or removed, accesses the chamber.

FIG. 72 is an illustration showing some of the features of an embodimentof a sampling module cartridge. The sampling module cartridge 668 has ahousing having an orientation sensitive contact interface for matingwith a complementary surface on the analyzer device. The contactinterface functions to align the sampling module cartridge with theanalyzer device, and also allows the analyzer device to rotate thesampling module cartridge in preparation for a new sampling event. Thecontact interface may take the form of cogs or grooves formed in thehousing, which mate with complementary cogs, or grooves in the chamberof the analyzer device.

The sampling module cartridge has a plurality of sampling sites 678 onthe housing, which are shown as slightly concave depressions near theperimeter of the sampling module cartridge 668. Each sampling sitedefines an opening 679 contiguous with a sample input port entering thesampling module. In an alternate embodiment, the sampling sites andsample input ports are located on the edge of the sampling modulecartridge. Optical windows 680 allow transmission of light into thesampling module cartridge for the purpose of optically reading testresults. Alternatively, sensor connection points allow transmission oftest results to the analyzer device via electrical contact. Access ports681, if present, allow transmission of force or pressure into thesampling module cartridge from the analyzer device. The access ports maybe useful in conjunction with running a calibration test or combiningreagents with sampled blood or other bodily fluids.

The described features are arranged around the sampling modulecartridge, and the sampling module cartridge is radially partitionedinto many sampling modules, each sampling module having the componentsnecessary to perform a single blood sampling and testing event. Aplurality of sampling modules are present on a sampling modulecartridge, generally at least ten sampling modules are present on asingle disposable sampling module cartridge; at least about 20, or moreon some embodiments, and at least about 34 sampling modules are presenton one embodiment, allowing the sampling module cartridge to bemaintained in the analyzer device for about a week before replacing witha new sampling module cartridge (assuming five sampling and testingevents per day for seven days). With increasing miniaturization, up toabout 100, or more preferably up to about 150, sampling modules may beincluded on a single sampling module cartridge, allowing up to a monthbetween replacements with new sampling module cartridges. It may benecessary for sampling sites to be located in several concentric ringsaround the sampling module cartridge or otherwise packed onto thehousing surface to allow the higher number of sampling modules on asingle sampling module cartridge.

In other embodiments, the sampling module cartridge may be any othershape which may conveniently be inserted into a analyzer device andwhich are designed to contain multiple sampling modules, e.g. a square,rectangular, oval, or polygonal shape. Each sampling module isminiaturized, being generally less than about 6.0 cm long by about 1.0cm wide by about 1.0 cm thick, so that thirty five more or lesswedge-shaped sampling modules can fit around a disk having a radius ofabout 6.0 cm. In some embodiments, the sampling modules can be muchsmaller, e.g. less than about 3.0 cm long by about 0.5 cm wide by about0.5 cm thick.

FIG. 73 depicts, in a highly schematic way, a single sampling module,positioned within the analyzer device. Of course, it will occur to theperson of ordinary skill in the art that the various recited componentsmay be physically arranged in various configurations to yield afunctional system. FIG. 73 depicts some components, which might only bepresent in alternate embodiments and are not necessarily all present inany single embodiment. The sampling module has a sample input port 682,which is contiguous with an opening 683 defined by a sampling site 684on the cartridge housing 685. A lancet 686 having a lancet tip 687adjacent to the sample input port 682 is operably maintained within thehousing such that the lancet 686 can move to extend the lancet tip 687through the sample input port 682 to outside of the sampling modulecartridge.

The lancet 686 also has a lancet head 688 opposite the lancet tip. Thelancet 686 driven to move by a lancet driver 689, which is schematicallydepicted as a coil around the lancet 686. The lancet driver 689optionally is included in the sampling module cartridge as pictured oralternatively is external to the sampling module cartridge. The samplingmodule may further include a driver port 690 defined by the housingadjacent to the lancet head 688—the driver port 690 allows an externallancet driver 691 access to the lancet 686.

In embodiments where the lancet driver 689 is in the sampling modulecartridge, it may be necessary to have a driver connection point 694upon the housing accessible to the analyzer device. The driverconnection point 694 may be a means of triggering the lancet driver 689or of supplying motive force to the lancet driver 689, e.g. anelectrical current to an electromechanical lancet driver. Note that anyof the drivers discussed above, including controllable drivers,electromechanical drivers, etc., can be substituted for the lancetdriver 689 shown.

In one embodiment a pierceable membrane 692 is present between thelancet tip 687 and the sample input port 682, sealing the lancet 686from any outside contact prior to use. A second membrane 693 may bepresent adjacent to the lancet head 688 sealing the driver port 690. Thepierceable membrane 692 and the second membrane 693 function to isolatethe lancet 686 within the lancet chamber to maintain sterility of thelancet 686 prior to use. During use the lancet tip 687 and the externallancet driver 691 pierce the pierceable membrane 692 and the secondmembrane 693, if present respectively.

A sample flow channel 695 leads from the sample input port 682 to ananalytical region 696. The analytical region 696 is associated with asample sensor capable of being read by the analyzer device. If thesample sensor is optical in nature, the sample sensor may includeoptically transparent windows 697 in the housing above and below theanalytical region 696, allowing a light source in the analyzer device topass light 698 through the analytical region. An optical sensor 698′,e.g. a CMOS array, is present in the analyzer device for sensing thelight 699 that has passed through the analytical region 696 andgenerating a signal to be analyzed by the analyzer device.

In a separate embodiment, only one optically transparent window ispresent, and the opposing side of the analytical region is silvered orotherwise reflectively coated to reflect light back through theanalytical region and out the window to be analyzed by the analyzerdevice. In an alternate embodiment, the sensor is electrochemical 700,e.g. an enzyme electrode, and includes a means of transmitting anelectric current from the sampling module cartridge to the analyzerdevice, e.g. an electrical contact 701, or plurality of electricalcontacts 701, on the housing accessible to the analyzer device.

In one embodiment, the pierceable membrane 692 may be made ofpolymer-based film that has been coated with a silicone-based gel. Forexample, the membrane structure may comprise a polymer-based filmcomposed of polyethylene terephthalate, such as the film sold under thetrademark MYLAR®. The membrane structure may further comprise a thincoating of a silicone-based gel such as the gel sold under the trademarkSYLGARD® on at least one surface of the film.

The usefulness of such a film is its ability to reseal after the lancettip has penetrated it without physically affecting the lancet's cuttingtip and edges. The MYLAR® film provides structural stability while thethin SYLGARD® silicone laminate is flexible enough to retain its formand close over the hole made in the MYLAR® film. Other similar materialsfulfilling the structural stability and flexibility roles may be used inthe manufacture of the pierceable membrane in this embodiment.

The pierceable membrane 692 operates to allow the lancet tip 687 topierce the pierceable membrane 692 as the lancet tip 687 travels intoand through the sampling port 682. In the described embodiment, thesilicone-based gel of the membrane 692 automatically seals the cutcaused by the lancet tip 687. Therefore, after an incision is made on afinger of a user and the lancet tip 687 is retracted back through thepierceable membrane 692, the blood from the incision is prevented fromflowing through the pierceable membrane 692, which aids the blood totravel through the sample flow channel 695 to accumulate within theanalytical region 696.

Thus the pierceable membrane 692 prevents blood from flowing into thelancet device assembly, and blood contamination and loss into the lancetdevice mechanism cavity are prevented. In yet another embodiment, usedsample input ports are automatically sealed off before going to the nextsample acquisition cycle by a simple button mechanism. A similarmechanism seals off a sample input port should sampling be unsuccessful.

In an alternate embodiment, a calibrant supply reservoir 702 is alsopresent in each sampling module. The calibrant supply reservoir 702 isfilled with a calibrant solution and is in fluid communication with acalibration chamber 703. The calibration chamber 703 provides a sourceof a known signal from the sampling module cartridge to be used tovalidate and quantify the test conducted in the analytical region 696.As such, the configuration of the calibration chamber 703 closelyresembles the analytical region 696.

During use, the calibrant solution is forced from the calibrant supplyreservoir 702 into the calibration chamber 703. The figure depicts astylized plunger 704 above the calibrant supply reservoir 702 ready tosqueeze the calibrant supply reservoir 702. In practice, a variety ofmethods of transporting small quantities of fluid are known in the artand can be implemented on the sampling module cartridge. The calibrationchamber 703 is associated with a calibrant testing means.

FIG. 73 shows two alternate calibrant testing means—optical windows 697and an electrochemical sensor 676. In cases where the sampling module isdesigned to perform several different tests on the blood, both opticaland electrochemical testing means may be present. The optical windows697 allow passage of light 677 from the analyzer device through thecalibration chamber 703, whereupon the light 703′ leaving thecalibration chamber 703 passes onto an optical sensor 698′ to result ina signal in the analyzer device.

The electrochemical sensor 676 is capable of generating a signal that iscommunicated to the analyzer device via, e g. an electrical contact704′, which is accessible to a contact probe 702′ on the analyzer devicethat can be extended to contact the electrical contact 704′. Thecalibrant solution may be any solution, which, in combination with thecalibrant testing means, will provide a suitable signal, which willserve as calibration measurement to the analyzer device. Suitablecalibrant solutions are known in the art, e.g. glucose solutions ofknown concentration. The calibration measurement is used to adjust theresults obtained from sample sensor from the analytical region 696.

To maintain small size in some sampling module cartridge embodiments,allowing small quantities of sampled blood to be sufficient, eachcomponent of the sampling module must be small, particularly the sampleflow channel and the analytical region. The sample flow channel can beless than about 0.5 mm in diameter, specifically less than about 0.3 mmin diameter, more specifically less than about 0.2mm in diameter, andeven more specifically less than about 0.1 mm in diameter.

The sample flow channel may generally be at least about 50 micrometersin diameter. The dimensions of the analytical region may be less thanabout 1 mm by about 1 mm by about 1 mm, specifically less than about 0.6mm by about 0.6 mm by about 0.4 mm, more specifically less than about0.4 mm by 0.4 mm by 0.2 mm, and even more specifically less than about0.2 mm by about 0.2 mm by about 0.1 mm. The analytical region cangenerally be at least about 100 micrometers by 100 micrometers by 50micrometers.

The sampling module cartridge is able to return a valid testing resultwith less than about 5 microliters of blood taken from the skin of apatient, specifically less than about 1 microliter, more specificallyless than about 0.4 microliters, and even more specifically less thanabout 0.2 microliters. Generally, at least 0.05 microliters of blood isdrawn for a sample.

The cartridge housing may be made in a plurality of distinct pieces,which are then assembled to provide the completed housing. The distinctpieces may be manufactured from a wide range of substrate materials.Suitable materials for forming the described apparatus include, but arenot limited to, polymeric materials, ceramics (including aluminum oxideand the like), glass, metals, composites, and laminates thereof.Polymeric materials are particularly preferred herein and will typicallybe organic polymers that are homopolymers or copolymers, naturallyoccurring or synthetic, crosslinked or uncrosslinked.

It is contemplated that the various components and devices describedherein, such as sampling module cartridges, sampling modules, housings,etc., may be made from a variety of materials, including materials suchas the following: polycarbonates; polyesters, including poly (ethyleneterephthalate) and poly(butylene terephthalate); polyamides, (such asnylons); polyethers, including polyformaldehyde and poly (phenylenesulfide); polyimides, such as that manufactured under the trademarksKAPTON (DuPont, Wilmington, Del.) and UPILEX (Ube Industries, Ltd.,Japan); polyolefin compounds, including ABS polymers, Kel-F copolymers,poly(methyl methacrylate), poly(styrene-butadiene) copolymers,poly(tetrafluoroethylene), poly(ethylenevinyl acetate) copolymers,poly(N-vinylcarbazole) and polystyrene.

The various components and devices described herein may also befabricated from a “composite,” i.e., a composition comprised of unlikematerials. The composite may be a block composite, e.g., an A-B-A blockcomposite, an A-B-C block composite, or the like. Alternatively, thecomposite may be a heterogeneous combination of materials, i.e., inwhich the materials are distinct from separate phases, or a homogeneouscombination of unlike materials. A laminate composite with severaldifferent bonded layers of identical or different materials can also beused.

Other preferred composite substrates include polymer laminates,polymer-metal laminates, e.g., polymer coated with copper, aceramic-in-metal or a polymer-in-metal composite. One composite materialis a polyimide laminate formed from a first layer of polyimide such asKAPTON polyimide, available from DuPont (Wilmington, Del.), that hasbeen co-extruded with a second, thin layer of a thermal adhesive form ofpolyimide known as KJ®, also available from DuPont (Wilmington, Del.).

Any suitable fabrication method for the various components and devicesdescribed herein can be used, including, but not limited to, molding andcasting techniques, embossing methods, surface machining techniques,bulk machining techniques, and stamping methods. Further,injection-molding techniques well known in the art may be useful inshaping the materials used to produce sample modules and othercomponents.

For some embodiments, the first time a new sampling module cartridge 668is used, the user removes any outer packaging material from the samplingmodule cartridge 668 and opens the lid 671 of the analyzer device 669,exposing the chamber. The sampling module cartridge 668 is slipped intothe chamber and the lid 671 closed. The patient's skin is positionedupon the sampling site 678 and the integrated process of lancing theskin, collecting the blood sample, and testing the blood sample isinitiated, e.g. by pressing a function button 674 to cause the lancetdriver to be triggered. The patient's skin is maintained in positionupon the sampling site 678, adjacent the sample input port 682, until anadequate volume of blood has been collected, whereupon the system mayemit a signal (e.g. an audible beep) that the patient's skin may belifted from the sampling site 678.

When the testing of the sample is complete, the analyzer device 669automatically reads the results from the sampling module cartridge 668and reports the results on the readout display 673. The analyzer device669 may also store the result in memory for later downloading to acomputer system. The sampling module cartridge 668 may thenautomatically be advanced to bring the next sampling module inline forthe next use. Each successive time the system is used (optionally untilthe sampling module cartridge 668 is used up), the patient's skin may beplaced upon the sampling site 678 of the (already installed) samplingmodule cartridge 668, thus simplifying the process of blood sampling andtesting.

A method of providing more convenient blood sampling, wherein a seriesof blood samples may be collected and tested using a single disposablesampling module cartridge which is designed to couple to an analyzerdevice is described. Embodiments of the sampling module cartridgeinclude a plurality of sampling modules. Each sampling module can beadapted to perform a single blood sampling cycle and is functionallyarranged within the sampling module cartridge to allow a new samplingmodule to be brought online after a blood sampling cycle is completed.

Each blood sampling cycle may include lancing of a patient's skin,collection of a blood sample, and testing of the blood sample. The bloodsampling cycle may also include reading of information about the bloodsample by the analyzer device, display and/or storage of test results bythe analyzer device, and/or automatically advancing the sampling modulecartridge to bring a new sampling module online and ready for the nextblood sampling cycle to begin.

A method embodiment starts with coupling of the sampling modulecartridge and analyzer device and then initiating a blood samplingcycle. Upon completion of the blood sampling cycle, the sampling modulecartridge is advanced to bring a fresh, unused sampling module online,ready to perform another blood sampling cycle. Generally, at least tensampling modules are present, allowing the sampling module cartridge tobe advanced nine times after the initial blood sampling cycle.

In some embodiments, more sampling modules are present and the samplingmodule cartridge may be advanced about 19 times, and about 34 times insome embodiments, allowing about 19 or about 34 blood sampling cycles,respectively, after the initial blood sampling cycle. After a series ofblood sampling cycles has been performed and substantially all (i.e.more than about 80%) of the sampling modules have been used, thesampling module cartridge is decoupled from the analyzer device anddiscarded, leaving the analyzer device ready to be coupled with a newsampling module cartridge.

Referring to FIGS. 74-76, a tissue penetration sampling device 180 isshown with the controllable driver 179 of FIG. 20 coupled to a samplingmodule cartridge 705 and disposed within a driver housing 706. A ratchetdrive mechanism 707 is secured to the driver housing 706, coupled to thesampling module cartridge 705 and configured to advance a samplingmodule belt 708 within the sampling module cartridge 705 so as to allowsequential use of each sampling module 709 in the sampling module belt708. The ratchet drive mechanism 707 has a drive wheel 711 configured toengage the sampling modules 709 of the sampling module belt 708. Thedrive wheel 711 is coupled to an actuation lever 712 that advances thedrive wheel 711 in increments of the width of a single sampling module709. A T-slot drive coupler 713 is secured to the elongated couplershaft 184.

A sampling module 709 is loaded and ready for use with the drive head198 of the lancet 183 of the sampling module 709 loaded in the T-slot714 of the drive coupler 713. A sampling site 715 is disposed at thedistal end 716 of the sampling module 709 disposed about a lancet exitport 717. The distal end 716 of the sampling module 709 is exposed in amodule window 718, which is an opening in a cartridge cover 721 of thesampling module cartridge 705. This allows the distal end 716 of thesampling module 709 loaded for use to be exposed to avoid contaminationof the cartridge cover 721 with blood from the lancing process.

A reader module 722 is disposed over a distal portion of the samplingmodule 709 that is loaded in the drive coupler 713 for use and has twocontact brushes 724 that are configured to align and make electricalcontact with sensor contacts 725 of the sampling module 709 as shown inFIG. 77. With electrical contact between the sensor contacts 725 andcontact brushes 724, the processor 193 of the controllable driver 179can read a signal from an analytical region 726 of the sampling module709 after a lancing cycle is complete and a blood sample enters theanalytical region 726 of the sampling module 709. The contact brushes724 can have any suitable configuration that will allow the samplingmodule belt 708 to pass laterally beneath the contact brushes 724 andreliably make electrical contact with the sampling module 709 loaded inthe drive coupler 713 and ready for use. A spring loaded conductive ballbearing is one example of a contact brush 724 that could be used. Aresilient conductive strip shaped to press against the inside surface ofthe flexible polymer sheet 727 along the sensor contact region 728 ofthe sampling module 709 is another embodiment of a contact brush 724.

The sampling module cartridge 705 has a supply canister 729 and areceptacle canister 730. The unused sampling modules of the samplingmodule belt 708 are disposed within the supply canister 729 and thesampling modules of the sampling module belt 708 that have been used areadvanced serially after use into the receptacle canister 730.

FIG. 77 is a perspective view of a section of the sampling module belt708 shown in the sampling module cartridge 705 in FIG. 74. The samplingmodule belt 708 has a plurality of sampling modules 709 connected inseries by a sheet of flexible polymer 727. The sampling module belt 708shown in FIG. 77 is formed from a plurality of sampling module bodyportions 731 that are disposed laterally adjacent each other andconnected and sealed by a single sheet of flexible polymer 727. Theflexible polymer sheet 727 can optionally have sensor contacts 725,flexible electrical conductors 732, sample sensors 733 or anycombination of these elements formed on the inside surface 734 of theflexible polymer sheet 727. These electrical, optical or chemicalelements can be formed by a variety of methods including vapordeposition and the like.

The proximal portion 735 of the flexible polymer sheet 727 has beenfolded over on itself in order to expose the sensor contacts 725 to theoutside surface of the sampling module 709. This makes electricalcontact between the contact brushes 724 of the reader module 722 and thesensor contacts 725 easier to establish as the sampling modules 709 areadvanced and loaded into position with the drive coupler 713 of thecontrollable driver 179 ready for use. The flexible polymer sheet 727can be secured to the sampling module body portion 731 by adhesivebonding, solvent bonding, ultrasonic thermal bonding or any othersuitable method.

FIG. 78 shows a perspective view of a single sampling module 709 of thesampling module belt 708 of FIG. 77 during the assembly phase of thesampling module 709. The proximal portion 735 of the flexible polymersheet 727 is being folded over on itself as shown in order to expose thesensor contacts 725 on the inside surface of the flexible polymer sheet727. FIG. 79 is a bottom view of a section of the flexible polymer sheet727 of the sampling module 709 of FIG. 78 illustrating the sensorcontacts 725, flexible conductors 732 and sample sensors 733 depositedon the bottom surface of the flexible polymer sheet 727.

A lancet 183 is shown disposed within the lancet channel 736 of thesampling module 709 of FIG. 78 as well as within the lancet channels 736of the sampling modules 709 of the sampling module belt 708 of FIG. 77.The lancet 183 has a tip 196 and a shaft portion 201 and a drive head198. The shaft portion 201 of the lancet slides within the lancetchannel 736 of the sampling module 709 and the drive head 198 of thelancet 183 has clearance to move in a proximal and distal directionwithin the drive head slot 737 of the sampling module 709. Disposedadjacent the drive head slot 737 and at least partially forming thedrive head slot are a first protective strut 737′ and a secondprotective strut 737″ that are elongated and extend substantiallyparallel to the lancet 183.

In one lancet 183 embodiment, the drive head 198 of the lancet 183 canhave a width of about 0.9 to about 1.1 mm. The thickness of the drivehead 198 of the lancet 183 can be about 0.4 to about 0.6 mm. The drivehead slot 714 of the sampling module 709 should have a width that allowsthe drive head 198 to move freely within the drive head slot 714. Theshaft portion 201 of the lancet 183 can have a transverse dimension ofabout 50 μm to about 1000 μm. Typically, the shaft portion 201 of thelancet 183 has a round transverse cross section, however, otherconfigurations are contemplated.

The sampling module body portions 731 and the sheet of flexible polymer727 can both be made of polymethylmethacrylate (PMMA), or any othersuitable polymer, such as those discussed above. The dimensions of atypical sampling module body portion 731 can be about 14 to about 18 mmin length, about 4 to about 5 mm in width, and about 1.5 to about 2.5 mmin thickness. In other embodiments, the length of the sample module bodyportion can be about 0.5 to about 2.0 inch and the transverse dimensioncan be about 0.1 to about 0.5 inch. The thickness of the flexiblepolymer sheet 727 can be about 100 to about 150 microns. The distancebetween adjacent sampling modules 709 in the sampling module belt 708can vary from about 0.1 mm to about 0.3 mm, and in some embodiments,from about 0.2 to about 0.6.

FIGS. 80 and 81 show a perspective view of the body portion 731 of thesampling module 709 of FIG. 77 without the flexible polymer cover sheet727 or lancet 183 shown for purposes of illustration. FIG. 81 is anenlarged view of a portion of the body portion 731 of the samplingmodule 709 of FIG. 80 illustrating the sampling site 715, sample inputcavity 715′, sample input port 741, sample flow channel 742, analyticalregion 743, control chamber 744, vent 762, lancet channel 736, lancetchannel stopping structures 747 and 748 and lancet guides 749-751 of thesampling module 709.

The lancet channel 736 has a proximal end 752 and a distal end 753 andincludes a series of lancet bearing guide portions 749-751 and sampleflow stopping structures 747-748. The lancet guides 749-751 may beconfigured to fit closely with the shaft of the lancet 183 and confinethe lancet 183 to substantially axial movement. At the distal end 753 ofthe lancet channel 736 the distal-most lancet guide portion 749 isdisposed adjacent the sample input port 741 and includes at itsdistal-most extremity, the lancet exit port 754 which is disposedadjacent the sample input cavity 715′. The sample input cavity can havea transverse dimension, depth or both, of about 2 to 5 times thetransverse dimension of the lancet 183, or about 0.2 to about 2 mm,specically, about 0.4 to about 1.5 mm, and more specifially, about 0.5to about 1.0 mm. The distal-most lancet guide 749 can have innertransverse dimensions of about 300 to about 350 microns in width andabout 300 to about 350 microns in depth. Proximal of the distal-mostlancet guide portion 749 is a distal sample flow stop 747 that includesa chamber adjacent the distal-most lancet 749. The chamber has atransverse dimension that is significantly larger than the transversedimension of the distal-most lancet guide 749. The chamber can have awidth of about 600 to about 800 microns, and a depth of about 400 toabout 600 microns and a length of about 2000 to about 2200 microns. Therapid transition of transverse dimension and cross sectional areabetween the distal-most lancet bearing guide 749 and the distal sampleflow stop 747 interrupts the capillary action that draws a fluid samplethrough the sample input cavity 715′ and into the lancet channel 736.

A center lancet bearing guide 750 is disposed proximal of the distallancet channel stop 747 and can have dimensions similar to those of thedistal-most lancet bearing guide 749. Proximal of the center lancetguide 750 is a proximal lancet channel stop 748 with a chamber. Thedimensions of the proximal lancet channel stop can be the same orsimilar to those of the distal lancet channel stop 747. The proximallancet channel stop 748 can have a width of about 600 to about 800microns, and a depth of about 400 to about 600 microns and a length ofabout 2800 to about 3000 microns. Proximal of the proximal lancetchannel stop 748 is a proximal lancet guide 751. The proximal lancetguide 751 can dimensions similar to those of the other lancet guide 749and 750 portions With inner transverse dimensions of about 300 to about350 microns in width and about 300 to about 350 microns in depth.Typically, the transverse dimension of the lancet guides 749-751 areabout 10 percent larger than the transverse dimension of the shaftportion 201 of the lancet 183 that the lancet guides 749-751 areconfigured to guide.

A proximal fracturable seal (not shown) can be positioned between theproximal lancet guide 751 and the shaft portion 201 of the lancet 183that seals the chamber of the proximal lancet channel stop 748 from theoutside environment. The fracturable seal seals the chamber of theproximal lancet channel stop 748 and other interior portions of thesample chamber from the outside environment when the sampling module 709is stored for use. The fracturable seal remains intact until the lancet183 is driven distally during a lancet cycle at which point the seal isbroken and the sterile interior portion of the sample chamber is exposedand ready to accept input of a liquid sample, such as a sample of blood.A distal fracturable seal (not shown) can be disposed between the lancet183 and the distal-most lancet guide 749 of the sampling module 709 toseal the distal end 753 of the lancet channel 736 and sample input port741 to maintain sterility of the interior portion of the sampling module709 until the lancet 183 is driven forward during a lancing cycle.

Adjacent the lancet exit port 754 within the sample input cavity 715′ isthe sample input port 741 that is configured to accept a fluid samplethat emanates into the sample input cavity 715′ from target tissue 233at a lancing site after a lancing cycle. The dimensions of the sampleinput port 741 can a depth of about 60 to about 70 microns, a width ofabout 400 to about 600 microns. The sample input cavity can have atransverse dimension of about 2 to about 5 times the transversedimension of the lancet 183, or about 400 to about 1000 microns. Thesample input cavity serves to accept a fluid sample as it emanates fromlanced tissue and direct the fluid sample to the sample input port 741and thereafter the sample flow channel 742. The sample flow channel 742is disposed between and in fluid communication with the sample inputport 741 and the analytical region 743. The transverse dimensions of thesample flow channel 742 can be the same as the transverse dimensions ofthe sample input port 741 with a depth of about 60 to about 70 microns,a width of about 400 to about 600 microns. The length of the sample flowchannel 742 can be about 900 to about 1100 microns. Thus, in use, targettissue is disposed on the sampling site 715 and a lancing cycleinitiated. Once the target tissue 233 has been lanced and the samplebegins to flow therefrom, the sample enters the sample input cavity 715′and then the sample input port 741. The sample input cavity 715′ may besized and configured to facilitate sampling success by applying pressureto a perimeter of target tissue 233 before, during and after the lancingcycle and hold the wound track open after the lancing cycle to allowblood or other fluid to flow from the wound track and into the sampleinput cavity 715′. From the sample input port 741, the sample in thendrawn by capillary or other forces through the sample flow channel 742and into the analytical region 743 and ultimately into the controlchamber 744. The control chamber 744 may be used to provide indirectconfirmation of a complete fill of the analytical region 743 by a samplefluid. If a fluid sample has been detected in the control chamber 744,this confirms that the sample has completely filled the analyticalregion 743. Thus, sample detectors may be positioned within the controlchamber 744 to confirm filling of the analytical region 743.

The analytical region 743 is disposed between and in fluid communicationwith the sample flow channel 742 and the control chamber 744. Theanalytical region 743 can have a depth of about 60 to about 70 microns,a width of about 900 to about 1100 microns and a length of about 5 toabout 6 mm. A typical volume for the analytical region 743 can be about380 to about 400 nanoliters. The control chamber 744 is disposedadjacent to and proximal of the analytical region 743 and can have atransverse dimension or diameter of about 900 to about 1100 microns anda depth of about 60 to about 70 microns.

The control chamber 744 is vented to the chamber of the proximal lancetchannel stop 748 by a vent that is disposed between and in fluidcommunication with the control chamber 744 and the chamber of theproximal lancet channel stop 748. Vent 762 can have transversedimensions that are the same or similar to those of the sample flowchannel 742 disposed between the analytical region 743 and the sampleinput port 741. Any of the interior surfaces of the sample input port741, sample flow channels 742 and 762, analytical region 743, vents 745or control chamber 744 can be coated with a coating that promotescapillary action. A hydrophilic coating such as a detergent is anexample of such a coating.

The analytical region 743 accommodates a blood sample that travels bycapillary action from the sampling site 715 through the sample inputcavity 715′ and into the sample input port 741, through the sample flowchannel 742 and into the analytical region 743. The blood can thentravel into the control chamber 744. The control chamber 744 andanalytical region 743 are both vented by the vent 762 that allows gasesto escape and prevents bubble formation and entrapment of a sample inthe analytical region 743 and control chamber 744. Note that, inaddition to capillary action, flow of a blood sample into the analyticalregion 743 can be facilitated or accomplished by application of vacuum,mechanical pumping or any other suitable method.

Once a blood sample is disposed within the analytical region 743,analytical testing can be performed on the sample with the resultstransmitted to the processor 193 by electrical conductors 732, opticallyor by any other suitable method or means. In some embodiments, it may bedesirable to confirm that the blood sample has filled the analyticalregion 743 and that an appropriate amount of sample is present in thechamber in order to carry out the analysis on the sample.

Confirmation of sample arrival in either the analytical region 743 orthe control chamber 744 can be achieved visually, through the flexiblepolymer sheet 727 which can be transparent. However, it may be desirablein some embodiments to use a very small amount of blood sample in orderto reduce the pain and discomfort to the patient during the lancingcycle. For sampling module 709 embodiments such as described here,having the sample input cavity 715′ and sample input port 741 adjacentthe lancet exit port 754 allows the blood sample to be collected fromthe patient's skin 233 without the need for moving the sampling module709 between the lancing cycle and the sample collection process. Assuch, the user does not need to be able to see the sample in order tohave it transferred into the sampling module 709. Because of this, theposition of the sample input cavity 715′ and the sample input port 741adjacent the lancet exit port 754 allows a very small amount of sampleto be reliably obtained and tested.

Samples on the order of tens of nanoliters, such as about 10 to about 50nanoliters can be reliably collected and tested with a sampling module709. This size of blood sample is too small to see and reliably verifyvisually. Therefore, it is necessary to have another method to confirmthe presence of the blood sample in the analytical region 743. Samplesensors 733, such as the thermal sample sensors discussed above canpositioned in the analytical region 743 or control chamber 744 toconfirm the arrival of an appropriate amount of blood sample.

In addition, optical methods, such as spectroscopic analysis of thecontents of the analytical region 743 or control chamber 744 could beused to confirm arrival of the blood sample. Other methods such aselectrical detection could also be used and these same detection methodscan also be disposed anywhere along the sample flow path through thesampling module 709 to confirm the position or progress of the sample(or samples) as it moves along the flow path as indicated by the arrows763 in FIG. 81. The detection methods described above can also be usefulfor analytical methods requiring an accurate start time.

The requirement for having an accurate start time for an analyticalmethod can in turn require rapid filling of an analytical region 743because many analytical processes begin once the blood sample enters theanalytical region 743. If the analytical region 743 takes too long tofill, the portion of the blood sample that first enters the analyticalregion 743 will have been tested for a longer time that the last portionof the sample to enter the analytical region 743 which can result ininaccurate results. Therefore, it may be desirable in thesecircumstances to have the blood sample flow first to a reservoir,filling the reservoir, and then have the sample rapidly flow all at oncefrom the reservoir into the analytical region 743.

In one embodiment of the sampling module 709, the analytical region 743can have a transverse cross section that is substantially greater than atransverse cross section of the control chamber 744. The change intransverse cross section can be accomplished by restrictions in thelateral transverse dimension of the control chamber 744 versus theanalytical region 743, by step decreases in the depth of the controlchamber 744, or any other suitable method. Such a step between theanalytical region 743 and the control chamber 744 is shown in FIG. 81.In such an embodiment, the analytical region 743 can behave as a samplereservoir and the control chamber 744 as an analytical region thatrequires rapid or nearly instantaneous filling in order to have aconsistent analysis start time. The analytical region 743 fills by aflow of sample from the sample flow channel 742 until the analyticalregion is full and the sample reaches the step decrease in chamber depthat the boundary with the control chamber 744. Once the sample reachesthe step decrease in cross sectional area of the control chamber 744,the sample then rapidly fills the control chamber 744 by virtue of theenhanced capillary action of the reduced cross sectional area of thecontrol chamber 744. The rapid filling of the control chamber allows anyanalytical process initiated by the presence of sample to be carried outin the control chamber 744 with a reliable start time for the analyticalprocess for the entire sample of the control chamber 744.

Filling by capillary force is passive. It can also be useful for sometypes of analytical testing to discard the first portion of a samplethat enters the sampling module 709, such as the case where there may beinterstitial fluid contamination of the first portion of the sample.Such a contaminated portion of a sample can be discarded by having ablind channel or reservoir that draws the sample by capillary actioninto a side sample flow channel (not shown) until the side sample flowchannel or reservoir in fluid communication therewith, is full. Theremainder of the sample can then proceed to a sample flow channeladjacent the blind sample flow channel to the analytical region 743.

For some types of analytical testing, it may be advantageous to havemultiple analytical regions 743 in a single sampling module 709. In thisway multiple iterations of the same type of analysis could be performedin order to derive some statistical information, e.g. averages,variation or confirmation of a given test or multiple tests measuringvarious different parameters could be performed in different analyticalregions 743 in the same sampling module 709 filled with a blood samplefrom a single lancing cycle.

FIG. 82 is an enlarged elevational view of a portion of an alternativeembodiment of a sampling module 766 having a plurality of small volumeanalytical regions 767. The small volume analytical regions 767 can havedimensions of about 40 to about 60 microns in width in both directionsand a depth that yields a volume for each analytical region 767 of about1 nanoliter to about 100 nanoliters, specifically about 10 nanoliters toabout 50 nanoliters. The array of small volume analytical regions 767can be filled by capillary action through a sample flow channel 768 thatbranches at a first branch point 769, a second branch point 770 and athird branch point 771. Each small volume analytical region 767 can beused to perform a like analytical test or a variety of different testscan be performed in the various analytical regions 767.

For some analytical tests, the analytical regions 767 must have maintaina very accurate volume, as some of the analytical tests that can beperformed on a blood sample are volume dependent. Some analyticaltesting methods detect glucose levels by measuring the rate or kineticof glucose consumption. Blood volume required for these tests is on theorder of about 1 to about 3 microliters. The kinetic analysis is notsensitive to variations in the volume of the blood sample as it dependson the concentration of glucose in the relatively large volume samplewith the concentration of glucose remaining essentially constantthroughout the analysis. Because this type of analysis dynamicallyconsumes glucose during the testing, it is not suitable for use withsmall samples, e.g. samples on the order of tens of nanoliters where theconsumption of glucose would alter the concentration of glucose.

Another analytical method uses coulomb metric measurement of glucoseconcentration. This method is accurate if the sample volume is less thanabout 1 microliter and the volume of the analytical region is preciselycontrolled. The accuracy and the speed of the method is dependent on thesmall and precisely known volume of the analytical region 767 becausethe rate of the analysis is volume dependent and large volumes slow thereaction time and negatively impact the accuracy of the measurement.

Another analytical method uses an optical fluorescence decay measurementthat allows very small sample volumes to be analyzed. This method alsorequires that the volume of the analytical region 767 be preciselycontrolled. The small volume analytical regions 767 discussed above canmeet the criteria of maintaining small accurately controlled volumeswhen the small volume analytical regions 767 are formed using precisionmanufacturing techniques. Accurately formed small volume analyticalregions 767 can be formed in materials such as PMMA by methods such asmolding and stamping. Machining and etching, either by chemical or laserprocesses can also be used. Vapor deposition and lithography can also beused to achieve the desired results.

The sampling modules 709 and 766 discussed above all are directed toembodiments that both house the lancet 183 and have the ability tocollect and analyze a sample. In some embodiments of a sampling module,the lancet 183 may be housed and a sample collected in a samplereservoir without any analytical function. In such an embodiment, theanalysis of the sample in the sample reservoir may be carried out bytransferring the sample from the reservoir to a separate analyzer. Inaddition, some modules only serve to house a lancet 183 without anysample acquisition capability at all. The body portion 774 of such alancet module 775 is shown in FIG. 83. The lancet module 775 has anouter structure similar to that of the sampling modules 709 and 766discussed above, and can be made from the same or similar materials.

A flexible polymer sheet 727 (not shown) can be used to cover the faceof the lancet module 775 and contain the lancet 183 in a lancet channel776 that extends longitudinally in the lancet module body portion 774.The flexible sheet of polymer 727 can be from the same material and havethe same dimensions as the flexible polymer sheet 727 discussed above.Note that the proximal portion of the flexible polymer sheet 727 neednot be folded over on itself because there are no sensor contacts 725 toexpose. The flexible polymer sheet 727 in such a lancet module 775serves only to confine the lancet 183 in the lancet channel 776. Thelancet module 775 can be configured in a lancet module belt, similar tothe sampling module belt 708 discussed above with the flexible polymersheet 727 acting as the belt. A drive head slot 777 is dispose proximalof the lancet channel 776.

With regard to the tissue penetration sampling device 180 of FIG. 74,use of the device 180 begins with the loading of a sampling modulecartridge 705 into the controllable driver housing 706 so as to couplethe cartridge 705 to the controllable driver housing 706 and engage thesampling module belt 708 with the ratchet drive 707 and drive coupler713 of the controllable driver 179. The drive coupler 713 can have aT-slot configuration such as shown in FIGS. 84 and 85. The distal end ofthe elongate coupler shaft 184 is secured to the drive coupler 713 whichhas a main body portion 779, a first and second guide ramp 780 and 781and a T-slot 714 disposed within the main body portion 779. The T-slot714 is configured to accept the drive head 198 of the lancet 183. Afterthe sampling module cartridge 705 is loaded into the controllable driverhousing 706, the sampling module belt 708 is advanced laterally untilthe drive head 198 of a lancet 183 of one of the sampling modules 709 isfed into the drive coupler 713 as shown in FIGS. 86-88. FIGS. 86-88 alsoillustrate a lancet crimp device 783 that bends the shaft portion 201 ofa used lancet 183 that is adjacent to the drive coupler 713. Thisprevents the used lancet 183 from moving out through the module body 731and being reused.

As the sampling modules 709 of the sampling module belt 708 are usedsequentially, they are advanced laterally one at a time into thereceptacle canister 730 where they are stored until the entire samplingmodule belt 708 is consumed. The receptacle canister 730 can then beproperly disposed of in accordance with proper techniques for disposalof blood-contaminated waste. The sampling module cartridge 705 allowsthe user to perform multiple testing operations conveniently withoutbeing unnecessarily exposed to blood waste products and need onlydispose of one cartridge after many uses instead of having to dispose ofa contaminated lancet 183 or module 709 after each use.

FIGS. 89 and 90 illustrate alternative embodiments of sampling modulecartridges. FIG. 89 shows a sampling module cartridge 784 in a carouselconfiguration with adjacent sampling modules 785 connected rigidly andwith sensor contacts 786 from the analytical regions of the varioussampling modules 785 disposed near an inner radius 787 of the carousel.The sampling modules 785 of the sampling module cartridge 784 areadvanced through a drive coupler 713 but in a circular as opposed to alinear fashion.

FIG. 90 illustrates a block of sampling modules 788 in a four by eightmatrix. The drive head 198 of the lancets 183 of the sampling modules789 shown in FIG. 90 are engaged and driven using a different methodfrom that of the drive coupler 713 discussed above. The drive heads 198of the lancets 183 have an adhesive coating 790 that mates with andsecures to the drive coupler 791 of the lancet driver 179, which can beany of the drivers, including controllable drivers, discussed above.

The distal end 792 of the drive coupler 791 contacts and sticks to theadhesive 790 of proximal surface of the drive head 198 of the lancet 183during the beginning of the lancet cycle. The driver coupler 791 pushesthe lancet 183 into the target tissue 237 to a desired depth ofpenetration and stops. The drive coupler 791 then retracts the lancet183 from the tissue 233 using the adhesive contact between the proximalsurface of the drive head 198 of the lancet 183 and distal end surfaceof the drive coupler 791, which is shaped to mate with the proximalsurface.

At the top of the retraction stroke, a pair of hooked members 793 whichare secured to the sampling module 789 engage the proximal surface ofthe drive head 198 and prevent any further retrograde motion by thedrive head 198 and lancet 183. As a result, the drive coupler 791 breaksthe adhesive bond with the drive head 198 and can then be advanced by anindexing operation to the next sampling module 789 to be used.

FIG. 91 is a side view of an alternative embodiment of a drive coupler796 having a lateral slot 797 configured to accept the L-shaped drivehead 798 of the lancet 799 that is disposed within a lancet module 800and shown with the L-shaped drive head 798 loaded in the lateral slot797. FIG. 92 is an exploded view of the drive coupler 796, lancet 799with L-shaped drive head 798 and lancet module 800 of FIG. 91. This typeof drive coupler 796 and drive head 798 arrangements could besubstituted for the configuration discussed above with regard to FIGS.84-88. The L-shaped embodiment of the drive head 798 may be a lessexpensive option for producing a coupling arrangement that allows serialadvancement of a sampling module belt or lancet module belt through thedrive coupler 796 of a lancet driver, such as a controllable lancetdriver 179.

For some embodiments of multiple lancing devices 180, it may bedesirable to have a high capacity-lancing device that does not require alancet module 775 in order to house the lancets 183 stored in acartridge. Eliminating the lancet modules 775 from a multiple lancetdevice 180 allows for a higher capacity cartridge because the volume ofthe cartridge is not taken up with the bulk of multiple modules 775.FIGS. 93-96 illustrate a high capacity lancet cartridge coupled to abelt advance mechanism 804. The belt advance mechanism 804 is secured toa controlled driver 179 housing which contains a controlledelectromagnetic driver.

The lancet cartridge 803 has a supply canister 805 and a receptaclecanister 806. A lancet belt 807 is disposed within the supply canister805. The lancet belt 807 contains multiple sterile lancets 183 with theshaft portion 201 of the lancets 183 disposed between the adhesivesurface 808 of a first carrier tape 809 and the adhesive surface 810 ofa second carrier tape 811 with the adhesive surfaces 808 and 810 pressedtogether around the shaft portion 201 of the lancets 183 to hold themsecurely in the lancet belt 807. The lancets 183 have drive heads 198which are configured to be laterally engaged with a drive coupler 713,which is secured to an elongate coupler shaft 184 of the controllabledriver 179.

The belt advance mechanism 804 includes a first cog roller 814 and asecond cog roller 815 that have synchronized rotational motion and areadvanced in unison in an incremental indexed motion. The indexed motionof the first and second cog rollers 814 and 815 advances the lancet belt807 in units of distance equal to the distance between the lancets 183disposed in the lancet belt 807. The belt advance mechanism 804 alsoincludes a first take-up roller 816 and a second take-up roller 817 thatare configured to take up slack in the first and second carrier tapes809 and 811 respectively.

When a lancet belt cartridge 803 is loaded in the belt advance mechanism804, a lead portion 818 of the first carrier tape 809 is disposedbetween a first cog roller 814 and a second cog roller 815 of the beltadvance mechanism 804. The lead portion 818 of the first carrier tape809 wraps around the outer surface 819 of the first turning roller 827,and again engages roller 814 with the cogs 820 of the first cog roller814 engaged with mating holes 821 in the first carrier tape 809. Thelead portion 818 of the first carrier tape 809 is then secured to afirst take-up roller 816. A lead portion 822 of the second carrier tape811 is also disposed between the first cog roller 814 and second cogroller 815 and is wrapped around an outer surface 823 of the secondturning roller 828, and again engages roller 815 with the cogs 826′ ofthe second cog roller 815 engaged in with mating holes 825 of the secondcarrier tape 811. The lead portion 822 of the second carrier tape 811 isthereafter secured to a second take-up roller 817.

As the first and second cog rollers 814 and 815 are advanced, theturning rollers 827 and 828 peel the first and second carrier tapes 809and 811 apart and expose a lancet 183. The added length or slack of theportions of the first and second carrier tapes 809 and 811 produced fromthe advancement of the first and second cog rollers 814 and 815 is takenup by the first and second take-up rollers 816 and 817. As a lancet 183is peeled out of the first and second carrier tapes 809 and 811, theexposed lancet 183 is captured by a lancet guide wheel 826′ of the beltadvance mechanism 804, shown in FIG. 96, which is synchronized with thefirst and second cog rollers 814 and 815. The lancet guide wheel 826′then advances the lancet 183 laterally until the drive head 198 of thelancet 183 is loaded into the drive coupler 713 of the controllabledriver 179. The controllable driver 179 can then be activated drivingthe lancet 183 into the target tissue 233 and retracted to complete thelancing cycle.

Once the lancing cycle is complete, the belt advance mechanism 804 canonce again be activated which rotates the lancet guide wheel 826 andadvances the used lancet 183 laterally and into the receptacle canister806. At the same time, a new unused lancet 183 is loaded into the drivecoupler 713 and readied for the next lancing cycle. This repeatingsequential use of the multiple lancing device 180 continues until alllancets 183 in the lancet belt 807 have been used and disposed of in thereceptacle canister 806. After the last lancet 183 has been consumed,the lancet belt cartridge 803 can then be removed and disposed ofwithout exposing the user to any blood contaminated materials. The beltadvance mechanism 804 can be activated by a variety of methods,including a motorized drive or a manually operated thumbwheel which iscoupled to the first and second cog rollers 814 and 815 and lancet guidewheel 826.

Although discussion of the devices described herein has been directedprimarily to substantially painless methods and devices for access tocapillary blood of a patient, there are many other uses for the devicesand methods. For example, the tissue penetration devices discussedherein could be used for substantially painless delivery of smallamounts of drugs, or other bioactive agents such as gene therapy agents,vectors, radioactive sources etc. As such, it is contemplated that thetissue penetration devices and lancet devices discussed herein could beused to delivery agents to positions within a patient's body as well astaking materials from a patient's body such as blood, lymph fluid,spinal fluid and the like. Drugs delivered may include analgesics thatwould further reduce the pain perceived by the patient upon penetrationof the patient's body tissue, as well as anticoagulants that mayfacilitate the successful acquisition of a blood sample upon penetrationof the patient's tissue.

Referring to FIGS. 97-101, a device for injecting a drug or other usefulmaterial into the tissue of a patient is illustrated. The ability tolocalize an injection or vaccine to a specific site within a tissue,layers of tissue or organ within the body can be important. For example,epithelial tumors can be treated by injection of antigens, cytokine, orcolony stimulating factor by hypodermic needle or high-pressureinjection sufficient for the antigen to enter at least the epidermis orthe dermis of a patient. Often, the efficacy of a drug or combinationdrug therapy depends on targeted delivery to localized areas thusaffecting treatment outcome.

The ability to accurately deliver drugs or vaccinations to a specificdepth within the skin or tissue layer may avoid wastage of expensivedrug therapies therefore impacting cost effectiveness of a particulartreatment. In addition, the ability to deliver a drug or other agent toa precise depth can be a clear advantage where the outcome of treatmentdepends on precise localized drug delivery (such as with the treatmentof intralesional immunotherapy). Also, rapid insertion velocity of ahypodermic needle to a precise predetermined depth in a patient's skinis expected to reduce pain of insertion of the needle into the skin.Rapid insertion and penetration depth of a hypodermic needle, or anyother suitable elongated delivery device suitable for penetratingtissue, can be accurately controlled by virtue of a position feedbackloop of a controllable driver coupled to the hypodermic needle.

FIG. 97 illustrates 901 distal end 901 of a hypodermic needle 902 beingdriven into layers of skin tissue 903 by an electromagnetic controllabledriver 904. The electromagnetic controllable driver 904 of FIG. 79 canhave any suitable configuration, such as the configuration ofelectromagnetic controllable drivers discussed above. The layers of skin903 being penetrated include the stratum corneum 905, the stratumlucidum 906, the stratum granulosum 907, the stratum spinosum 908, thestratum basale 909 and the dermis 911. The thickness of the stratumcorneum 905 is typically about 300 micrometers in thickness. The portionof the epidermis excluding the stratum corneum 905 includes the stratumlucidum 906, stratum granulosum 907, and stratum basale can be about 200micrometers in thickness. The dermis can be about 1000 micrometers inthickness. In FIG. 97, an outlet port 912 of the hypodermic needle 902is shown disposed approximately in the stratum spinosum 908 layer of theskin 903 injecting an agent 913 into the stratum spinosum 908.

FIGS. 98-101 illustrate an agent injection module 915 including aninjection member 916, that includes a collapsible canister 917 and thehypodermic needle 902, that may be driven or actuated by a controllabledriver, such as any of the controllable drivers discussed above, todrive the hypodermic needle into the skin 903 for injection of drugs,vaccines or the like. The agent injection module 915 has a reservoir,which can be in the form of the collapsible canister 917 having a mainchamber 918, such as shown in FIG. 98, for the drug or vaccine 913 to beinjected. A cassette of a plurality of agent injection modules 915 (notshown) may provide a series of metered doses for long-term medicationneeds. Such a cassette may be configured similarly to the modulecassettes discussed above. Agent injection modules 915 and needles 902may be disposable, avoiding biohazard concerns from unspent drug or usedhypodermic needles 902. The geometry of the cutting facets 921 of thehypodermic needle shown in FIG. 79, may be the same or similar to thegeometry of the cutting facets of the lancet 183 discussed above.

Inherent in the position and velocity control system of some embodimentsof a controllable driver is the ability to precisely determine theposition or penetration depth of the hypodermic needle 902 relative tothe controllable driver or layers of target tissue or skin 903 beingpenetrated. For embodiments of controllable drivers that use opticalencoders for position sensors, such as an Agilent HEDS 9200 series, andusing a four edge detection algorithm, it is possible to achieve an inplane spatial resolution of +/−17 μm in depth. If a total tissuepenetration stroke is about 3 mm in length, such as might be used forintradermal or subcutaneous injection, a total of 88 position points canbe resolved along the penetration stroke. A spatial resolution this fineallows precise placement of a distal tip 901 or outlet port 912 of thehypodermic needle 902 with respect to the layers of the skin 903 duringdelivery of the agent or drug 913. In some embodiments, a displacementaccuracy of better than about 200 microns can be achieved, in others adisplacement accuracy of better than about 40 microns can be achieved.

The agent injection module 915 includes the injection member 916 whichincludes the hypodermic needle 902 and drug reservoir or collapsiblecanister 917, which may couple to an elongated coupler shaft 184 via adrive coupler 185 as shown. The hypodermic needle 902 can be driven to adesired penetration depth, and then the drug or other agent 913, such asa vaccine, is passed into an inlet port 922 of the needle 902 through acentral lumen 923 of the hypodermic needle 902 as shown by arrow 924,shown in FIG. 98, and out of the outlet port 912 at the distal end 901of the hypodermic needle 902, shown in FIG. 97.

Drug or agent delivery can occur at the point of maximum penetration, orfollowing retraction of the hypodermic needle 902. In some embodiments,it may be desirable to deliver the drug or agent 913 during insertion ofthe hypodermic needle 902. Drug or agent delivery can continue as thehypodermic needle 902 is being withdrawn (this is commonly the practiceduring anesthesia in dental work). Alternatively drug delivery can occurwhile the needle 902 is stationary during any part of the retractionphase.

The hollow hypodermic needle 902 is fitted with the collapsible canister917 containing a drug or other agent 913 to be dispensed. The walls 928of this collapsible canister 917 can be made of a soft resilientmaterial such as plastic, rubber, or any other suitable material. Adistal plate 925 is disposed at the distal end 926 of the collapsiblecanister is fixed securely to the shaft 927 of the hypodermic needleproximal of the distal tip 901 of the hypodermic needle 902. The distalplate 925 is sealed and secured to the shaft 927 of the hypodermicneedle 902 to prevent leakage of the medication 913 from the collapsiblecanister 917.

A proximal plate 931 disposed at a proximal end 932 of the collapsiblecanister 917 is slidingly fitted to a proximal portion 933 of the shaft927 of the hypodermic needle 902 with a sliding seal 934. The slidingseal 934 prevents leakage of the agent or medication 913 between theseal 934 and an outside surface of the shaft 927 of the hypodermicneedle 902. The sliding seal allows the proximal plate 931 of thecollapsible canister 917 to slide axially along the needle 902 relativeto the distal plate 925 of the collapsible canister 917. A drug dose maybe loaded into the main chamber 918 of the collapsible canister 917during manufacture, and the entire assembly protected during shippingand storage by packaging and guide fins 935 surrounding the drive headslot 936 of the agent injection module 915.

An injection cycle may begin when the agent injection module 915 isloaded into a ratchet advance mechanism (not shown), and registered at adrive position with a drive head 937 of the hypodermic needle 902engaged in the drive coupler 185. The position of the hypodermic needle902 and collapsible canister 917 in this ready position is shown in FIG.99.

Once the drive head 937 of the agent injection module 915 is loaded intothe driver coupler 185, the controllable driver can then be used tolaunch the injection member 916 including the hypodermic needle 902 andcollapsible canister 917 towards and into the patient's tissue 903 at ahigh velocity to a pre-determined depth into the patient's skin or otherorgan. The velocity of the injection member 916 at the point of contactwith the patient's skin 903 or other tissue can be up to about 10 metersper second for some embodiments, specifically, about 2 to about 5 m/s.In some embodiments, the velocity of the injection member 916 may beabout 2 to about 10 m/s at the point of contact with the patient's skin903. As the collapsible canister 917 moves with the hypodermic needle902, the proximal plate 931 of the collapsible canister 917 passesbetween two latch springs 938 of module body 939 that snap in behind theproximal plate 931 when the collapsible canister 917 reaches the end ofthe penetration stroke, as shown in FIG. 100.

The controllable driver then reverses, applies force in the oppositeretrograde direction and begins to slowly (relative to the velocity ofthe penetration stroke) retract the hypodermic needle 902. Thehypodermic needle 902 slides through the sliding seal 934 of thecollapsible canister 917 while carrying the distal plate 925 of thecollapsible canister with it in a proximal direction relative to theproximal plate 931 of the collapsible canister 917. This relative motionbetween the distal plate 925 of the collapsible canister 917 and theproximal plate 931 of the collapsible canister 917 causes the volume ofthe main chamber 918 to decrease. The decreasing volume of the mainchamber 918 forces the drug or other agent 913 disposed within the mainchamber 918 of the collapsible canister 917 out of the main chamber 918into the inlet port 922 in the shaft 927 of the hypodermic needle 902.The inlet port 922 of the hypodermic needle 902 is disposed within an influid communication with the main chamber 918 of the collapsiblecanister 917 as shown in FIG. 80. The drug or agent then passes throughthe central lumen 923 of the hollow shaft 927 of the hypodermic needle902 and is then dispensed from the output port 912 at the distal end 901of the hypodermic needle 902 into the target tissue 903. The rate ofperfusion of the drug or other agent 913 may be determined by an insidediameter or transverse dimension of the collapsible canister 917. Therate of perfusion may also be determined by the viscosity of the drug oragent 913 being delivered, the transverse dimension or diameter of thecentral lumen 923, the input port 922, or the output port 912 of thehypodermic needle 902, as well as other parameters.

During the proximal retrograde retraction stroke of the hypodermicneedle 902, drug delivery continues until the main chamber 918 of thecollapsible canister 917 is fully collapsed as shown in FIG. 101. Atthis point, the drive coupler 185 may continue to be retracted until thedrive head 937 of the hypodermic needle 902 breaks free or the distalseal 941 between the distal plate 925 of the chamber and the hypodermicneedle 902 fails, allowing the drive coupler 185 to return to a startingposition. The distal tip 901 of the hypodermic needle 902 can be drivento a precise penetration depth within the tissue 903 of the patientusing any of the methods or devices discussed above with regard toachieving a desired penetration depth using a controllable driver or anyother suitable driver.

In another embodiment, the agent injection module 915 is loaded into aratchet advance mechanism that includes an adjustable or movable distalstage or surface (not shown) that positions the agent injection 915module relative to a skin contact point or surface 942. In this way, anagent delivery module 915 having a penetration stroke of predeterminedfixed length, such as shown in FIGS. 99-101, reaches a pre-settablepenetration depth. The movable stage remains stationary during a drugdelivery cycle. In a variation of this embodiment, the moveable stagemotion may be coordinated with a withdrawal of the hypodermic needle 902to further control the depth of drug delivery.

In another embodiment, the latch springs 938 shown in the agentinjection module 915 of FIGS. 99-101 may be molded with a number ofratchet teeth (not shown) that engage the proximal end 932 of thecollapsible canister 917 as it passes by on the penetration stroke. Ifthe predetermined depth of penetration is less than the full stroke, theintermediate teeth retain the proximal end 932 of the collapsiblecanister 917 during the withdrawal stroke in order to collapse the mainchamber 918 of the collapsible canister 917 and dispense the drug oragent 913 as discussed above.

In yet another embodiment, drive fingers (not shown) are secured to anactuation mechanism (not shown) and replace the latch springs 938. Theactuation mechanism is driven electronically in conjunction with thecontrollable driver by a processor or controller, such as the processor60 discussed above, to control the rate and amount of drug deliveredanywhere in the actuation cycle. This embodiment allows the delivery ofmedication during the actuation cycle as well as the retraction cycle.

Inherent in the position and velocity control system of a controllabledriver is the ability to precisely define the position in space of thehypodermic needle 902, allowing finite placement of the hypodermicneedle in the skin 903 for injection of drugs, vaccines or the like.Drug delivery can be discrete or continuous depending on the need.

FIGS. 102-106 illustrate an embodiment of a cartridge 945 that may beused for sampling that has both a lancet cartridge body 946 and ansampling cartridge body 947. The sampling cartridge body 947 includes aplurality of sampling module portions 948 that are disposed radiallyfrom a longitudinal axis 949 of the sampling cartridge body 947. Thelancet cartridge body 946 includes a plurality of lancet module portions950 that have a lancet channel 951 with a lancet 183 slidably disposedtherein. The lancet module portions 950 are disposed radially from alongitudinal axis 952 of the lancet cartridge body 946.

The sampling cartridge body 947 and lancet cartridge body 946 aredisposed adjacent each other in an operative configuration such thateach lancet module portion 950 can be readily aligned in a functionalarrangement with each sampling module portion 948. In the embodimentshown in FIGS. 102-106, the sampling cartridge body 947 is rotatablewith respect to the lancet cartridge body 946 in order to align anylancet channel 951 and corresponding lancet 183 of the lancet cartridgebody 946 with any of the lancet channels 953 of the sampling moduleportions 948 of the sampling cartridge body 947. The operativeconfiguration of the relative location and rotatable coupling of thesampling cartridge body 947 and lancet cartridge body 946 allow readyalignment of lancet channels 951 and 953 in order to achieve afunctional arrangement of a particular lancet module portion 950 andsampling module portion 948. For the embodiment shown, the relativemotion used to align the particular lancet module portions 950 andsampling module portions 948 is confined to a single degree of freedomvia relative rotation.

The ability of the cartridge 945 to align the various sampling module948 portions and lancet module portions 950 allows the user to use asingle lancet 183 of a particular lancet module portion 950 withmultiple sampling module portions 948 of the sampling cartridge body947. In addition, multiple different lancets 183 of lancet moduleportions 950 could be used to obtain a sample in a single samplingmodule portion 948 of the sampling cartridge body 947 if a fresh unusedlancet 183 is required or desired for each lancing action and previouslancing cycles have been unsuccessful in obtaining a usable sample.

FIG. 102 shows an exploded view in perspective of the cartridge 945,which has a proximal end portion 954 and a distal end portion 955. Thelancet cartridge body 946 is disposed at the proximal end portion 954 ofthe cartridge 945 and has a plurality of lancet module portions 950,such as the lancet module portion 950 shown in FIG. 103. Each lancetmodule portion 950 has a lancet channel 951 with a lancet 183 slidablydisposed within the lancet channel 951. The lancet channels 951 aresubstantially parallel to the longitudinal axis 952 of the lancetcartridge body 946. The lancets 183 shown have a drive head 198, shaftportion 201 and sharpened tip 196. The drive head 198 of the lancets areconfigured to couple to a drive coupler (not shown), such as the drivecoupler 185 discussed above.

The lancets 183 are free to slide in the respective lancet channels 951and are nominally disposed with the sharpened tip 196 withdrawn into thelancet channel 951 to protect the tip 196 and allow relative rotationalmotion between the lancet cartridge body 946 and the sampling cartridgebody 947 as shown by arrow 956 and arrow 957 in FIG. 102. The radialcenter of each lancet channel 951 is disposed a fixed, known radialdistance from the longitudinal axis 952 of the lancet cartridge body 946and a longitudinal axis 958 of the cartridge 945. By disposing eachlancet channel 951 a fixed known radial distance from the longitudinalaxes 952 and 958 of the lancet cartridge body 946 and cartridge 945, thelancet channels 951 can then be readily and repeatably aligned in afunctional arrangement with lancet channels 953 of the samplingcartridge body 947. The lancet cartridge body 946 rotates about aremovable pivot shaft 959 which has a longitudinal axis 960 that iscoaxial with the longitudinal axes 952 and 950 of the lancet cartridgebody 946 and cartridge 945.

The sampling cartridge body 947 is disposed at the distal end portion955 of the cartridge and has a plurality of sampling module portions 948disposed radially about the longitudinal axis 949 of the samplingcartridge body 947. The longitudinal axis 949 of the sampling cartridgebody 947 is coaxial with the longitudinal axes 952, 958 and 960 of thelancet cartridge body 946, cartridge 945 and pivot shaft 959. Thesampling cartridge body 947 may also rotate about the pivot shaft 959.In order to achieve precise relative motion between the lancet cartridgebody 946 and the sampling cartridge body 947, one or both of thecartridge bodies 946 and 947 must be rotatable about the pivot shaft959, however, it is not necessary for both to be rotatable about thepivot shaft 959, that is, one of the cartridge bodies 946 and 947 may besecured, permanently or removably, to the pivot shaft 959.

The sampling cartridge body 947 includes a base 961 and a cover sheet962 that covers a proximal surface 963 of the base forming a fluid tightseal. Each sampling module portion 948 of the sampling cartridge body947, such as the sampling module portion 948 shown in FIG. 104 (withoutthe cover sheet for clarity of illustration), has a sample reservoir 964and a lancet channel 953. The sample reservoir 964 has a vent 965 at anoutward radial end that allows the sample reservoir 964 to readily fillwith a fluid sample. The sample reservoir 964 is in fluid communicationwith the respective lancet channel 953 which extends substantiallyparallel to the longitudinal axis 949 of the sampling cartridge body947. The lancet channel 953 is disposed at the inward radial end of thesample reservoir 964.

The lancet channels 953 of the sample cartridge body 947 allow passageof the lancet 183 and also function as a sample flow channel 966extending from an inlet port 967 of the lancet channel 953, shown inFIG. 106, to the sample reservoir 964. Note that a proximal surface 968of the cover sheet 962 is spatially separated from a distal surface 969of the lancet cartridge body 946 at the lancet channel site in order toprevent any fluid sample from being drawn by capillary action into thelancet channels 951 of the lancet cartridge body 946. The spatialseparation of the proximal surface 968 of the cover sheet 962 from thedistal surface 969 of the lancet cartridge body 946 is achieved with aboss 970 between the two surfaces 968 and 969 that is formed into thedistal surface 969 of the lancet cartridge body as shown in FIG. 105.

The sample reservoirs 964 of the sampling cartridge body 947 may includeany of the sample detection sensors, testing sensors, sensor contacts orthe like discussed above with regard to other sampling moduleembodiments. The cover sheet 962 may be formed of PMMA and haveconductors, sensors or sensor contacts formed on a surface thereof. Itmay also be desirable to have the cover sheet 962 made from atransparent or translucent material in order to use optical sensing ortesting methods for samples obtained in the sample reservoirs. In theembodiment shown, the outer radial location of at least a portion of thesample reservoirs 964 of the sampling cartridge body 967 is beyond anouter radial dimension of the lancet cartridge body 946. Thus, anoptical detector or sensor 971, such as shown in FIG. 105, can detect ortest a sample disposed within a sample reservoir 964 by transmitting anoptical signal through the cover sheet 962 and receiving an opticalsignal from the sample.

The cartridge bodies 946 and 947 may have features, dimensions ormaterials that are the same as, or similar to, features, dimensions ormaterials of the sampling cartridges and lancet cartridges, or anycomponents thereof, discussed above. The module portions 948 and 950 mayalso have features, dimensions or materials that are the same as, orsimilar to, features, dimensions or materials of the lancet or samplingmodules, or any components thereof, discussed above. In addition, thecartridge 945 can be coupled to, or positioned adjacent any of thedrivers discussed above, or any other suitable driver, in an operativeconfiguration whereby the lancets of the lancet cartridge body can beselectively driven in a lancing cycle. Although the embodiment shown inFIGS. 102-106 allows for alignment of various sampling module portions948 and lancet module portions 950 with relative rotational movement,other embodiments that function similarly are also contemplated. Forexample, lancet module portions, sampling module portions or both, couldbe arranged in a two dimensional array with relative x-y motion beingused to align the module portions in a functional arrangement. Suchrelative x-y motion could be accomplished with position sensors andservo motors in such an alternative embodiment order to achieve thealignment.

Other embodiments of the invention will be apparent to those skilled inthe art from consideration of the specification and practice of theinvention disclosed herein. It is intended that the specification andexamples be considered as exemplary only, with a true scope and spiritof the invention being indicated by the appended claims.

1. A method of measuring penetration depth of a lancet during a lancingcycle comprising: (a) driving the lancet toward the patient's targettissue; (b) using a processor to determine if the lancet has madecontact with a patient's skin by measuring for a sudden reduction invelocity of the lancet due to friction or resistance imposed on thelancet by the patient's skin and determine a contact point of the lancetwith the target tissue; (c) after determining the contact point,advancing the lancet out of a housing into the target tissue to aposition of maximum penetration and removing substantially all forceimparted from a lancet driver to the lancet at the position of maximumpenetration; (d) reading position of the lancet relative to the contactpoint during rearward displacement of the lancet due to elastic recoilof target tissue after the force from the lancet driver is removedwherein the lancet remains at the position of maximum penetration;measuring an amount of elastic tenting of the tissue; and furthercomprising measuring a magnitude of inelastic tenting of the tissue. 2.The method of claim 1 wherein the value of the magnitude of theinelastic tenting is about 100 to about 200 microns.
 3. The method ofclaim 1 wherein the contact point of the lancet with the target tissuecomprises measuring the deceleration of the lancet.